Biomedical subjects

K L Goa

Publications and source records attributed to K L Goa.

178 records · Page 10Linked to original sources

PubMed1988

Quazepam. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in insomnia.

Quazepam is a trifluoroethyl benzodiazepine hypnotic with a half-life of 27 to 41 hours, which has been shown to induce and maintain sleep in the short to long term (up to 4 weeks) treatment of patients with chronic or transient insomnia. Although its hypnotic efficacy has been well characterised against placebo, there are few clinical studies in comparison with established hypnotics, particularly over long term administration. However, preliminary evidence suggests that quazepam 15 to 30 mg is as effective as flurazepam and triazolam in usual therapeutic doses, and causes minimal rebound insomnia following its withdrawal, unlike rapidly eliminated benzodiazepines such as triazolam. The lack of rebound phenomena is likely to be attributable to the 'carryover' effects occurring after discontinuation of quazepam, which has pharmacologically active metabolites with half-lives of elimination similar to or longer than that of the parent drug. Probably because of the long half-lives of quazepam's metabolites, daytime sedation, fatigue and lethargy are the most frequently reported side effects. These side effects are most intense with the 30 mg dose and least with the 7.5mg dose, which has not been studied extensively. Hence, quazepam is an effective hypnotic which may be particularly suitable for short or medium term use in patients in whom withdrawal effects or rebound insomnia may be especially bothersome. Further definition of certain characteristics of its profile--such as its long term use and potential for development of tolerance or dependence, effects on psychomotor skills, efficacy of the 7.5mg dose, and suitability in elderly patients and patients with chronic organic diseases--will assist in more clearly defining its ultimate place in therapy.

Anti-Anxiety Agents↗

PubMed1988

Flumazenil. A preliminary review of its benzodiazepine antagonist properties, intrinsic activity and therapeutic use.

Flumazenil, a 1,4-imidazobenzodiazepine, is a specific benzodiazepine antagonist which is indicated for use when the effect of a benzodiazepine must be quickly attenuated or terminated. Following intravenous administration, the onset of clinically apparent benzodiazepine antagonism usually occurs within 1 to 5 minutes. Although flumazenil has a short elimination half-life of about 1 hour, a single intravenous dose of up to 1 mg is usually sufficient to attain and maintain for about 2 hours the desired level of consciousness after general anaesthesia or conscious to moderate sedation induced by benzodiazepines. After intoxication with high doses of benzodiazepines the initial single dose of flumazenil will require supplementing with repeated low intravenous doses or an infusion (0.1 mg/h) to maintain a state of wakefulness. Flumazenil is well tolerated, and since it reliably attenuates or reverses the central effects of benzodiazepines and is specific for these drugs, it facilitates diagnosis by eliminating benzodiazepine intoxication in patients in whom the cause of unconsciousness is unknown. While results of some studies suggested that flumazanil may have intrinsic benzodiazepine partial agonist or inverse agonist activity, this is unlikely to be clinically important with usual doses. Thus, flumazenil is a very promising, effective, short acting benzodiazepine antagonist which is well tolerated by most patients. Undoubtedly, its full clinical potential has yet to be realised.

Animals↗

PubMed1988

Cisapride. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use as a prokinetic agent in gastrointestinal motility disorders.

Cisapride, a substituted piperidinyl benzamide chemically related to metoclopramide, is an orally administered prokinetic agent which facilitates or restores motility throughout the length of the gastrointestinal tract. Its novel mechanism of action is thought to involve enhancement of acetylcholine release in the myenteric plexus of the gut. Because of its specificity cisapride is devoid of central depressant or antidopaminergic effects; side effects such as diarrhoea or loose stools, which occur infrequently, are related to its primary pharmacological action. Evidence exists from comparisons with placebo in initial trials to establish the efficacy of cisapride in improving healing rates and symptoms in patients with reflux oesophagitis, in alleviating symptoms in patients with non-ulcer dyspepsia, and in accelerating gastric emptying in gastroparesis. There are less conclusive data regarding the efficacy of cisapride in relieving symptoms in patients with gastroparesis, although preliminary results support a role for cisapride in certain groups such as diabetics. Limited data suggest that patients with chronic constipation due to underlying motility disorders may benefit from cisapride. Unfortunately, there is a paucity of trials comparing the efficacy of cisapride with other therapeutic agents. Thus, the relative position of cisapride in therapy cannot be defined at present. Should future results support preliminary evidence of comparable efficacy to metoclopramide, domperidone and ranitidine (in oesophagitis), cisapride with its favourable tolerability profile should claim a prominent position in the therapy of patients with a variety of gastrointestinal motility disorders.

Cisapride↗

PubMed1987

Nitrendipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of hypertension.

Nitrendipine is a calcium entry blocker shown to inhibit the movement of calcium through the 'slow channel' of cardiac and vascular smooth muscle, thus inducing peripheral vasodilation with consequent reductions in elevated blood pressure. As evidenced by clinical trials, nitrendipine promptly lowers blood pressure in patients with mild to moderate hypertension, and sustains this effect during long term administration. Combining nitrendipine with other antihypertensive agents such as diuretics or beta-blockers often results in successful treatment in patients unresponsive to nitrendipine monotherapy. Headache, oedema, flushing and palpitations commonly occurring during treatment with nitrendipine are generally mild, usually subsiding with continued therapy. Thus, although additional long term studies are required to properly assess the relative merits of the drug compared with other antihypertensives, by providing the clinician with an effective and safe alternative to traditional therapies, nitrendipine represents a step forward in the treatment of mild to moderate hypertension.

Humans↗

PubMed1987

Pentamidine isethionate. A review of its antiprotozoal activity, pharmacokinetic properties and therapeutic use in Pneumocystis carinii pneumonia.

Pentamidine isethionate, an aromatic diamidine, is an antiprotozoal agent proven to decrease mortality from Pneumocystis carinii pneumonia in debilitated infants and immunodeficient adults and children. Like the combination antimicrobial agent co-trimoxazole, pentamidine has been shown in retrospective studies to resolve episodes of pneumonia in approximately 41 to 87% of patients, including those with the acquired immunodeficiency syndrome (AIDS), when used alone or as sequential therapy. Although about 45% of all patients given pentamidine experience side effects--which may include nephrotoxicity, hypotension, hypoglycaemia or local reactions--in patients with AIDS the incidence of side effects is less with pentamidine than with co-trimoxazole. Thus, despite its profile of potentially severe side effects, pentamidine isethionate is a proven antimicrobial agent with a distinct place in the treatment of Pneumocystis carinii pneumonia in the growing population of AIDS patients.

Amidines↗

PubMed1987

l-Carnitine. A preliminary review of its pharmacokinetics, and its therapeutic use in ischaemic cardiac disease and primary and secondary carnitine deficiencies in relationship to its role in fatty acid metabolism.

l-Carnitine occurs naturally as an essential cofactor of fatty acid metabolism which is synthesised endogenously or obtained from dietary sources. In patients with primary carnitine deficiencies, which may be life-threatening, and some secondary deficiencies such as organic acidurias, the exogenously administered compound is clearly beneficial: by abolishing hypotonia, motor skills are improved, as are muscle weakness and wasting. In preliminary clinical trials in patients with ischaemic cardiac disease, therapy with l-carnitine has shown beneficial effects on myocardial function and metabolism and has improved exercise tolerance in patients with angina pectoris-findings which require further substantiation in larger controlled studies. Moreover, while some interesting evidence suggests that l-carnitine may find potential use in such diverse conditions as carnitine deficiencies secondary to prolonged total parenteral nutrition supplementation or chronic haemodialysis, hyperlipidaemias and the prevention of toxicity induced by anthracyclines and valproate, such findings must be regarded as preliminary. Exogenously administered l-carnitine is very well tolerated. Thus, while its role in primary deficiencies is established, with its profile of negligible toxicity l-carnitine is worthy of further investigation to more clearly define its therapeutic applications in a variety of conditions which may be indirectly related to alterations in fatty acid metabolism.

Carnitine↗

PubMed1987

Enprostil. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of peptic ulcer disease.

Enprostil, a synthetic analogue of prostaglandin E2, is effective in the treatment of patients with duodenal or gastric ulcers. As demonstrated in pharmacological studies in healthy volunteers and in patients with inactive ulcer disease, gastric acid secretion is suppressed by up to 80% for almost 12 hours after single doses of enprostil. The drug also reduces the secretion of pepsin, another 'aggressive' factor in peptic ulcer disease. Interestingly, in contrast to the H2-receptor antagonists, which either increase or have no effect on serum gastrin concentrations, enprostil inhibits basal and postprandial gastrin release. Although the possible effects of enprostil on 'defensive' factors in peptic ulcer disease-which are thought to protect the mucosa-require much further clarification, some evidence obtained in man indicates that bicarbonate secretion is enhanced by enprostil. Further, data from animal studies suggest that microvascular integrity may be preserved by a direct action of enprostil on the gastric mucosa. In healthy volunteers, the administration of enprostil in antisecretory doses protects the gastric mucosa against of enprostil in antisecretory doses protects the gastric mucosa against aspirin-induced injury. Cumulative rates of ulcer healing observed in patients with duodenal ulcers after 4 weeks' treatment with enprostil 35 micrograms twice daily were about 50 to 80%, which were similar to those seen in comparative trials with usual therapeutic doses of cimetidine or pirenzepine, but less than occurred with ranitidine. Moreover, enprostil has been shown to relieve daytime pain in a similar percentage of patients as do these H2-receptor antagonists, but night-time pain appears to respond less well to therapy with the prostaglandin. As evidenced by a few controlled trials in patients with gastric ulcers, treatment with enprostil 35 micrograms twice daily for 6 weeks provides ulcer healing in parallel with pain relief as effectively as cimetidine and ranitidine in a high percentage of patients (about 80% after 6 weeks). Prophylactic treatment with enprostil after initial ulcer healing has reduced the rate of duodenal ulcer relapse in patients 'at risk', but to a lesser extent than has ranitidine. Gastrointestinal symptoms-abdominal cramping and pain, flatulence, nausea and notably, diarrhoea-are the most frequently reported side effects during therapy with enprostil. Diarrhoea occurs in about 10% of patients, but is rarely of a severity necessitating treatment discontinuation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Zopiclone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy as an hypnotic.

Zopiclone is the first of the cyclopyrrolones, a new class of psychotherapeutic agents possessing a pharmacological profile of high efficacy and low toxicity similar to that of the benzodiazepines. Binding is thought to occur to the benzodiazepine receptor complex, or to a site closely linked to this complex. Although zopiclone exhibits anticonvulsant, muscle relaxant and anxiolytic properties in animals, it finds better use as an hypnotic because of marked sedating effects. In clinical trials, zopiclone (usually 7.5 mg) improved sleep in chronic insomniacs similarly to nitrazepam 5 mg, flurazepam 15 to 30 mg, triazolam 0.5 mg and temazepam 20 mg, but in a single study was slightly less effective than flunitrazepam 2 mg in some evaluation criteria. Sleep induction before surgical procedures in hospitalised patients is satisfactory with zopiclone, but when the drugs are administered a few hours before surgery, diazepam appears to be more effective in alleviating preoperative anxiety. Minimal impairment of psychomotor skills and mental acuity occurs in the morning after a bedtime dose of zopiclone, which has a short half-life of about 5 hours and no long acting metabolites. No serious side effects have been reported in the relatively small number of patients studied to date; the development of 'bitter taste' does not deter patients from continuing therapy. Thus, with its short duration of action zopiclone is a useful alternative to other hypnotics, especially in patients intolerant of residual effects the morning after taking an hypnotic.

Anti-Anxiety Agents↗

PubMed1986

Buspirone. A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic.

Buspirone hydrochloride (HCl)1 is a new anxiolytic with a unique chemical structure. Its mechanism of action remains to be elucidated. Unlike the benzodiazepines, buspirone lacks hypnotic, anticonvulsant and muscle relaxant properties, and hence has been termed 'anxioselective'. As evidenced by a few double-blind clinical trials, buspirone 15 to 30 mg/day improves symptoms of anxiety assessed by standard rating scales similarly to diazepam, clorazepate, alprazolam and lorazepam. Like diazepam, buspirone is effective in patients with mixed anxiety/depression, although the number of patients studied to date is small. In several studies, a 'lagtime' of 1 to 2 weeks to the onset of anxiolytic effect has been noted; hence motivation of patient compliance may be necessary. Sedation occurs much less often after buspirone than after the benzodiazepines; other side effects are minor and infrequent. In healthy volunteers, buspirone does not impair psychomotor or cognitive function, and appears to have no additive effect with alcohol. Early evidence suggests that buspirone has limited potential for abuse and dependence. Thus, although only wider clinical use for longer periods of time will more clearly define some elements of its pharmacological profile, with its low incidence of sedation buspirone is a useful addition to the treatments available for generalised anxiety. It may well become the preferred therapy in patients in whom daytime alertness is particularly important.

Animals↗

PubMedDate not supplied

Ocular diclofenac. A review of its pharmacology and clinical use in cataract surgery, and potential in other inflammatory ocular conditions.

Diclofenac sodium is a potent nonsteroidal anti-inflammatory drug with analgesic activity. When instilled as a topical 0.1% solution in a limited number of patients undergoing cataract surgery, diclofenac limits surgically induced miosis, reduces signs of ocular inflammation, does not cause elevations in intraocular pressure, and reduces the occurrence and severity of cystoid macular oedema. Preliminary findings suggest a niche for topical diclofenac in other ocular inflammatory conditions such as iritis, episcleritis and conjunctivitis, although its efficacy in these areas awaits confirmation. The drug appears well tolerated, apart from a transient burning sensation after instillation in some patients. Ocular diclofenac thus appears well suited as a local anti-inflammatory adjunct to cataract surgery, and may be useful in some other inflammatory ocular conditions.

Animals↗

PubMedDate not supplied

Epalrestat. A review of its pharmacology, and therapeutic potential in late-onset complications of diabetes mellitus.

Epalrestat is a carboxylic acid derivative which inhibits aldose reductase, an enzyme of the sorbitol (polyol) pathway. Under hyperglycaemic conditions epalrestat reduces intracellular sorbitol accumulation, which has been implicated in the pathogenesis of late-onset complications of diabetes mellitus. Epalrestat 150 mg/day for 12 weeks improved motor and sensory nerve conduction velocity, and vibration threshold compared with baseline and placebo in patients with diabetic neuropathy. Subjective symptoms including pain, numbness, hyperaesthesia, coldness in the extremities, muscular weakness, dizziness, and orthostatic fainting were also improved. Similar benefits were seen in a comparison with historical controls. Epalrestat 300 mg/day for 1 or 3 years was also significantly superior to placebo or no treatment in improving electroretinogram parameters and photo stress recovery time in patients with diabetic retinopathy. Improvements were also documented by funduscopy and fluorescein angiography. Epalrestat appeared most effective in patients with less severe diabetes mellitus and more recent development of late-onset complications. Epalrestat is apparently well tolerated with predominantly minor adverse events reported in clinical trials. Liver enzyme elevations were most commonly reported but generally resolved spontaneously on dose reduction or discontinuation. The effects of age and renal impairment on the efficacy and tolerability of epalrestat require clarification, and data on its use in other late-onset complications of diabetes such as nephropathy are also lacking. Comparisons with other aldose reductase inhibitors are also required to fully determine the role of epalrestat. The suggested ability of epalrestat to prevent the onset of diabetic complications should also be investigated. Thus, available data suggest epalrestat produces some improvement in the late-onset neuropathy and retinopathy associated with diabetes mellitus, although additional trials are required to determine whether ongoing therapy is necessary to maintain the improvements achieved and to confirm tolerability in the long term. Nevertheless, preliminary results suggest that epalrestat may be a useful drug in an area where there is a need for effective therapy.

Aged↗

PubMedDate not supplied

Denileukin diftitox.

Denileukin diftitox is a novel interleukin-2 receptor (IL-2R)-targeted diphtheria toxin. It binds to cells expressing IL-2R and inhibits protein synthesis through internalization of the diphtheria toxin fragment. In patients with IL-2R-positive cutaneous T cell lymphoma (CTCL), the overall response rate was 23 and 36%, respectively, after denileukin diftitox 9 or 18 micrograms/kg/day for 5 days every 3 weeks and was 37% in a dose-ranging trial. Quality of life (QOL) improved significantly in patients with CTCL who responded to treatment with denileukin diftitox 9 or 18 micrograms/kg/day compared with QOL at baseline and in nonresponders. In a murine model of IL-2R-expressing malignancy, denileukin diftitox prolonged survival compared with controls. The most common adverse events reported in patients who received denileukin diftitox were hypoalbuminemia, fever/chills, acute hypersensitivity reactions, nausea/vomiting and asthenia. Vascular leak syndrome has occurred during denileukin diftitox therapy. Antibody titers to denileukin diftitox occur in most patients after treatment but the presence of antibodies does not preclude a clinical response.

Animals↗

PubMedDate not supplied

Sevoflurane in paediatric anaesthesia: a review.

UNLABELLED: Sevoflurane is an ether inhalation anaesthetic agent with low pungency, a non-irritant odour and a low blood: gas partition coefficient. It can be rapidly and conveniently administered without discomfort, and its low solubility facilitates precise control over the depth of anaesthesia and a rapid and smooth induction of, and emergence from, general anaesthesia. As an induction and maintenance agent for ambulatory and nonambulatory surgery in children, sevoflurane provides more rapid induction of, and emergence from, anaesthesia than halothane, and has similar or better patient acceptability. Time to discharge from the recovery area is usually at least as fast with sevoflurane as with halothane. While rapid emergence from sevoflurane lessens the time spent under anaesthesia, postoperative pain may be more intense and occur earlier than during more gradual emergence. Sevoflurane has been used successfully as an induction agent for tracheal intubation and laryngeal mask airway (LMA) insertion: time to LMA insertion is faster with sevoflurane than halothane, but the 2 drugs provide similar conditions for tracheal intubation. The pattern and incidence of induction and emergence events such as cough, laryngospasm and agitation/excitement is similar with sevoflurane and halothane; however, sevoflurane may cause less postoperative nausea and vomiting. At present, differences have not been consistently shown between the 2 drugs in their propensity to cause postoperative excitement or agitation. Compared with halothane, sevoflurane has low potential for arrhythmogenicity. Clinical experience does not substantiate concerns over the potential nephrotoxicity of the sevoflurane byproducts pentafluoroisopropenyl fluoromethyl ether ('Compound A') and plasma F- ions; no renal impairment has been documented in children receiving sevoflurane in clinical trials. The potential for sevoflurane hepatotoxicity also appears negligible. There are few trials comparing sevoflurane with agents other than halothane in paediatric anaesthesia. As well, pharmacoeconomic analyses are scarce and incompletely published; further studies are needed to determine whether shortened times to emergence will translate into cost savings. CONCLUSION: Sevoflurane is a preferred anaesthetic agent for induction and maintenance of paediatric anaesthesia because of its rapid induction and recovery characteristics, lack of pungency and agreeable odour, and acceptable cardiovascular profile. Although the issue of postoperative excitement requires clarification, sevoflurane anaesthesia can be considered a rational choice for ambulatory and nonambulatory surgery in children.

Anesthesia, Inhalation↗

PubMedDate not supplied

Calfactant: a review of its use in neonatal respiratory distress syndrome.

UNLABELLED: Calfactant (Infasurt) is a natural bovine surfactant which has been evaluated for intratracheal use in the prevention and rescue treatment of respiratory distress syndrome (RDS) in preterm infants. In 2 randomised, double-blind, multicentre clinical trials of prophylactic use, calfactant 100 or 105 mg phospholipid per kg bodyweight (mg/kg) reduced RDS incidence, RDS severity and mortality rates to a greater extent than colfosceril palmitate (Exosurf Neonatal) 67.5 mg/kg and was generally similar to beractant (Survanta) 100 mg/kg. Although the rate of mortality before discharge from hospital was significantly higher in infants with birthweights <600 g who received calfactant than in those who received beractant, this may not be a typical result. As rescue treatment, calfactant 100 or 105 mg/kg reduced RDS severity, but not mortality rates, significantly more than colfosceril palmitate 67.5 mg/kg or beractant 100 mg/kg in 2 randomised, double-blind, multicentre clinical trials. In addition, the duration of effect of calfactant as prophylaxis or rescue treatment appeared to be longer than that of beractant. In other randomised trials, prophylaxis was more effective than rescue treatment with calfactant, particularly in infants of < or =29 weeks gestational age. The incidence of pulmonary air leak events was lower with calfactant than with colfosceril palmitate (12 vs 22%) but was identical with calfactant and beractant (15% with either agent). The incidence of other complications associated with RDS was usually similar with all 3 agents in clinical trials in preterm infants. The incidence of intraventricular haemorrhage was significantly higher in 1 clinical trial, and that of septicaemia was significantly lower in another, with calfactant versus colfosceril palmitate, but the combined incidences of these complications was similar with the 2 agents when results from different trials were pooled. The incidence of acute adverse events (i.e. those which occurred during administration of the drug) with calfactant was similar to that with beractant and higher than that with colfosceril palmitate; the difference may been related to reduced RDS severity in calfactant versus colfosceril palmitate recipients. Acute adverse events were usually transient and not severe. CONCLUSIONS: Calfactant is a well tolerated natural bovine surfactant which is effective in the prevention and treatment of RDS in preterm infants. Further investigation is needed to more clearly determine the efficacy and tolerability of calfactant relative to that of other surfactant preparations. When more data are available, it is likely that calfactant will be useful as an alternative to beractant (at least in infants of birthweights >600 g), and calfactant may be preferred over colfosceril palmitate in both the prophylaxis and treatment of RDS.

Biological Products↗

PubMedDate not supplied

Lamotrigine. A review of its use in childhood epilepsy.

UNLABELLED: Lamotrigine is an antiepileptic agent that blocks use-dependent voltage-sensitive sodium channels, thereby preventing excitatory neurotransmitter release. However, this mechanism does not explain the broad range of clinical efficacy of this agent. In noncomparative trials, adjunctive lamotrigine (< or = 15 mg/kg/day) improved seizure control in children and adolescents with various refractory seizure types, with about 29 to 90% of patients showing a > or = 50% reduction in seizure frequency after > or = 3 months' treatment. Lamotrigine was particularly effective in generalised seizures, especially absence seizures and those related to the Lennox-Gastaut syndrome. In one placebo-controlled study, 33% of children and young adults (aged 3 to 25 years) with refractory Lennox-Gastaut syndrome had a reduction in seizure frequency of > or = 50% after 16 weeks of adjunctive lamotrigine treatment, compared with 16% of placebo recipients (p = 0.01). Significant reductions in seizure frequency when compared with placebo were also observed in patients with refractory generalised and partial seizures. The use of lamotrigine has also been associated with beneficial effects on cognition and behaviour. Adverse events associated with lamotrigine are primarily neurological, gastrointestinal and dermatological and are typically mild or moderate and transient with the exception of a potentially serious rash. Maculopapular or erythematous skin rash occurred in approximately 12% of paediatric patients (aged < 16 years) treated with lamotrigine and was the most common reason for treatment discontinuation. More severe forms of rash, including Stevens-Johnson syndrome, occasionally occurred, with a 3-fold higher incidence in children (approximately 1%) than adults (approximately 0.3%). However, lamotrigine treatment in paediatric trials was generally given at higher initial doses and faster dose escalations than recently revised recommendations. These factors, as well as concomitant use of valproic acid (valproate sodium), are associated with an increased risk of rash. CONCLUSION: Although published clinical evidence is still limited in paediatric populations, lamotrigine is an effective and generally well tolerated broad-spectrum agent for adjunctive treatment of refractory seizures in children, most notably in those with Lennox-Gastaut syndrome. Results of direct comparisons with other antiepileptic agents are needed to determine more clearly the place of lamotrigine, particularly relative to newer agents, in the treatment of childhood epilepsy. The potential for serious rash in recipients of lamotrigine should also be kept in mind. Nonetheless, lamotrigine is a welcome addition to the available treatments for refractory childhood epilepsy, particularly Lennox-Gastaut syndrome.

Adolescent↗

PubMedDate not supplied

Diphtheria-tetanus-acellular pertussis vaccine adsorbed (Triacelluvax; DTaP3-CB): a review of its use in the prevention of Bordetella pertussis infection.

UNLABELLED: DTaP3-CB (Triacelluvax) is an acellular pertussis (aP) vaccine containing 3 antigens from purified Bordetella pertussis bacteria combined with diphtheria and tetanus toxoids (DT). In addition to purified filamentous haemagglutinin and pertactin, DTaP3-CB contains pertussis toxin which has been genetically rather than chemically detoxified. As shown in randomised, double-blind clinical trials in infants, DTaP3-CB elicits an immune response similar to or greater than that of whole cell (DTwP) vaccines. Results of a large multicentre study comparing DTaP3-CB with 12 acellular and 1 DTwP vaccine indicate that DTaP3-CB, like all acellular vaccines, induces variable immune responses to different pertussis antigens; however, antibody titres to pertussis toxin are normally higher after immunisation with the genetically detoxified vaccine than with other 3- or 4-component vaccines. When given as a fourth or fifth booster dose, DTaP3-CB produced a significant immune response in infants primed with 3 doses of either a DTaP or DTwP vaccine. Virtually all infants immunised with DTaP3-CB had a serological response to diphtheria and tetanus toxoids. Data from 2 very large efficacy studies indicate that DTaP3-CB has high and long lasting protective efficacy against culture-confirmed pertussis which is greater than that of a 2-component vaccine (DTaP2-SB) and the whole cell DTwP-CON vaccine after a 3-, 5- and 12-month immunisation schedule and after a 2-, 4- and 6-month schedule with the DTwP-CON vaccine. However, the DTwP-CON whole cell vaccine has been noted for its low immunogenicity in 1 study and low efficacy and immunogenicity in another study. On the other hand, DTaP3-CB vaccine has similar efficacy to DTaP3-SB (after immunisation at 2, 4 and 6 months), DTaP5-CON and DTwP-EVANS against culture-confirmed pertussis with > or =21 days cough in infants immunised according to a 3-, 5- and 12-month schedule. Infants immunised with DTaP3-CB experienced significantly fewer adverse events such as pain, redness, swelling and irritability than infants given DTwP. DTaP3-CB has a similar tolerability profile to other acellular vaccines and is associated with similar rates of local tenderness, irritability, fever (> or =40 degrees C) and persistent crying. Comparative trials have shown that infants immunised with DTaP3-CB had a lower incidence of pain at the site of injection and fever (> or =38 degrees C) compared with other acellular vaccines, although this may have little clinical significance. Concomitant administration of DTaP3-CB with hepatitis B, oral polio or Haemophilus influenzae type B vaccines did not affect the immunogenicity of these other paediatric vaccines. CONCLUSION: Data from clinical trials with DTaP3-CB vaccine indicate that this vaccine induces high and long lasting efficacy. It is at least as efficacious as most whole cell vaccines and generally similar in efficacy to the most efficacious acellular pertussis vaccines containing 3 or more pertussis antigens. DTaP3-CB is better tolerated than whole cell vaccines and has a similar tolerability profile to other acellular vaccines; the possible lower risk of severe adverse events remains to be confirmed. The low reactogenicity of DTaP3-CB is likely to make it well tolerated and therefore well accepted for the immunisation of infants, thereby enabling wider implementation of vaccination programmes.

Bordetella pertussis↗