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Biomedical subjects

P S Collier

Publications and source records attributed to P S Collier.

At least 37 records · Page 2Linked to original sources
PubMed1989

Does pretreatment with cimetidine and ranitidine affect the disposition of bupivacaine?

Thirty patients who chose extradural analgesia for elective Caesarean section were pretreated, by random selection, with cimetidine 400 mg, ranitidine 150 mg or no H2-blocker. Following the administration of 0.5% bupivacaine, no significant difference was found between peak plasma bupivacaine concentrations or area under the plasma bupivacaine concentration-time curve (AUC) in these three groups. This study shows that a single dose of cimetidine or ranitidine does not affect significantly the disposition of bupivacaine in the obstetric patient.

Adult↗
PubMed1989

Clinical and pharmacokinetic aspects of ciprofloxacin in the treatment of acute exacerbations of pseudomonas infection in cystic fibrosis patients.

Twelve cystic fibrosis patients, aged over 18, who had developed an acute respiratory exacerbation and who had Pseudomonas species isolated from their sputum, were entered into a clinical trial involving ciprofloxacin. The dosage regimen was 100 mg iv followed by 500 mg twice daily orally if less than 40 kg in weight and 200 mg iv followed by 750 mg twice daily orally if greater than 40 kg. Ciprofloxacin was well tolerated with no major side effects, except in one patient who withdrew after onset of headaches and generalized aches and pains. Eleven of the 12 patients showed clinical improvement at the end of the treatment period as determined by weight gain, Shwachman Score, Chrispin Norman Score and pulmonary function tests. MICs of Pseudomonas species isolated from the sputum at the start of the trial were in the range 0.25-4 mg/l. During therapy, sensitivity of isolates decreased and did not return to starting levels at the end of a four week follow-up period. Pharmacokinetic parameters were similar to those reported for fasting healthy volunteers by other workers except for bioavailability which was reduced in the non-fasting patients.

Administration, Oral↗
PubMed1989

Effect of intravenous cimetidine on lignocaine disposition during extradural caesarean section.

We studied whether an intravenous bolus of cimetidine altered the disposition of extradurally administered lignocaine in the parturient. Mothers who requested extradural analgesia for elective Caesarean section were randomly pretreated with either cimetidine 200 mg intravenously (n = 5) or no H2-receptor antagonist (n = 5). No difference was found between peak plasma lignocaine levels or area under the plasma concentration/time curve between the two groups after administration of 6 mg/kg lignocaine 2% with adrenaline 1:200,000. There was no evidence for an effect of a single intravenous dose of cimetidine on lignocaine disposition in the obstetric patient. In addition, the extradural administration of 6 mg/kg lignocaine produces plasma levels well below toxic levels.

Anesthesia, Epidural↗
PubMed1989

Single dose oral H2-antagonists do not affect plasma lidocaine levels in the parturient.

We studied whether a single oral dose of either cimetidine or ranitidine affects the disposition of epidurally administered lidocaine in the parturient. Patients given epidural analgesia for elective caesarean section were randomly pretreated with either cimetidine 400 mg (n = 5), ranitidine 150 mg (n = 7) or no H2 receptor antagonist (n = 5). Following the administration of 400 mg of lidocaine 2% with adrenaline 1:200,000 no difference was found in peak plasma lidocaine levels or area under the plasma concentration/time curve (AUC) between the three groups. A single oral dose of cimetidine or ranitidine does not affect lidocaine disposition in the obstetric patient.

Anesthesia, Epidural↗
PubMed1988

A pharmacokinetic study of midazolam in paediatric patients undergoing cardiac surgery.

Midazolam 0.3 mg kg-1 was given as a single dose to three groups of children undergoing cardiac surgery to determine its pharmacokinetic profile in this situation. The first group, undergoing closed heart surgery, received the midazolam during the operation. The other groups underwent cardiopulmonary bypass (CPB) with and without complete circulatory arrest. Mean clearance was 512 ml kg-1 h-1 and mean elimination half-lives were 3.3 h following CPB, with a tendency to a higher clearance in those children who had not undergone bypass. In a subsequent part of the study, 10 children received an infusion of midazolam 0.05 mg kg-1 h-1, in combination with intermittent doses of morphine, in the postoperative period. Mean plasma midazolam concentrations consistent with adequate sedation were 80-100 ng ml-1 during the infusion. One child who had not undergone CPB had very low plasma concentrations of midazolam with the same rate of infusion, consistent with the tendency for higher clearance in this group in the bolus pharmacokinetic study.

Cardiac Surgical Procedures↗
PubMed1988

Effect of ciprofloxacin in an in-vitro pharmacokinetic model against Pseudomonas aeruginosa isolated during cystic fibrosis lung infection.

An in-vitro pharmacokinetic model was used to simulate ciprofloxacin concentrations in serum observed in vivo following oral doses of 250, 500 and 750 mg, in a culture of Pseudomonas aeruginosa isolated from the sputum of a cystic fibrosis patient. In the 12 h interval following each dose, a period of bactericidal activity was observed, succeeded by bacteriostasis and subsequent bacterial regrowth. In all cases bacterial regrowth was first observed when the ciprofloxacin concentration in the culture flask of the dynamic model fell below the MIC. For the three doses investigated, the surviving bacteria at the end of each 12-h dosing interval showed an increase in MIC compared with that of the culture before ciprofloxacin exposure. The post-antibiotic effect of ciprofloxacin against P. aeruginosa was observed for 1-5 h, and was dose related.

Ciprofloxacin↗
PubMed1987

Cimetidine and ranitidine increase midazolam bioavailability.

Cimetidine has been shown to inhibit the oxidative metabolism of a variety of low- and high-extraction drugs. Despite the findings of initial investigators, there is evidence that ranitidine may exert similar effects. Eight healthy volunteer subjects took part in a within-subject crossover study. They received midazolam, 15 mg, by mouth after pretreatment with cimetidine, ranitidine, or nothing and midazolam, 10 mg, intravenously on separate occasions. Mean absolute bioavailability of midazolam was increased by more than 30% after cimetidine (P less than 0.01) and 26% after ranitidine (P less than 0.05). The data, which agree with a concurrent clinical study indicating greater hypnotic action of midazolam after ranitidine, indicate that this is not a result of enhanced midazolam absorption and that reduced hepatic clearance is the most likely explanation.

Absorption↗
PubMed1987

Midazolam sedation following open heart surgery.

Midazolam given as hourly intermittent injections was compared with the same dose given by infusion for postoperative sedation in patients after cardiopulmonary bypass. A stable concentration was rapidly attained with the infusion whereas 6-8 h was required to attain stable plasma (trough) concentrations in the intermittent injection group. Plasma concentrations decreased rapidly to low values within 6 h of discontinuation of therapy. High plasma concentrations and a long (16 h) half-life were noted in one patient who may be a slow metabolizer of the drug.

Adult↗
PubMed1987

A comparison of the early pharmacokinetics of midazolam in pregnant and nonpregnant women.

The early pharmacokinetics of midazolam were compared in pregnant (active labour, awaiting and during elective Caesarean section) and matched gynaecological patients scheduled to undergo elective hysterectomy, half of whom were given an oxytocin infusion. A standard dose of 5 mg was given intravenously. For the first 15 minutes patients in labour had significantly higher plasma midazolam levels compared to all other groups. This was associated with the largest area under the curve (2 hours), the smallest volume of distribution and lowest clearance. Midazolam when given immediately before Caesarean section, can result in depression of the infant.

Apgar Score↗
PubMed1986

Prolonged midazolam elimination half-life.

The pharmacokinetics of a fixed dose of midazolam (0.3 mg kg-1 i.v.) were studied in detail in 115 healthy patients or volunteers and nine were found with a prolonged elimination half-life. A further 102 patients had an abbreviated pharmacokinetic study, of whom five showed a similar abnormality. Defective hepatic metabolism of midazolam may be a factor in the aetiology of what appears to be a true phenomenon, occurring in 6% of over 200 fit subjects given a standard dose of the drug.

Benzodiazepines↗
PubMed1986

Bioavailability of three formulations of intravenous diazepam.

It has been generally assumed that the bioavailability of different formulations of intravenous diazepam is identical. In a within-subject crossover study using eight healthy volunteers, we have found that both the initial and the overall plasma diazepam levels are significantly lower after both emulsion (Diazemuls) and micelle preparations than after an organic formulation (Valium). These findings are relevant to the interpretation of the results of past, present and future clinical studies involving intravenous diazepam. The studies with Valium and Diazemuls confirm the clinical impression of the lesser potency of the latter formulation.

Adult↗
PubMed1985

Age and nature of operation influence the pharmacokinetics of midazolam.

The pharmacokinetics of midazolam were studied in surgical patients given 0.3 mg kg-1 i.v. for either the induction of anaesthesia, or postoperative sedation following cardiopulmonary bypass. The short elimination half-life of midazolam (2.4 h in patients less than 50 yr undergoing minor surgery) was significantly, although not markedly, prolonged with age (4.1 h in patients greater than 50 yr undergoing minor procedures) and by the nature of the operation (3.8 h after major operative procedures). These changes were the result of alterations in clearance and volume of distribution with age, and in volume of distribution with nature of operation.

Adult↗
PubMed1985

Influence of plasma proteins on the onset of hypnotic action of intravenous midazolam.

The action of midazolam is influenced by serum protein binding as seen in the relationship between the time of onset of action of a fixed dose of the drug and the plasma albumin. Pretreatment with intravenous aspirin produces a decrease in the in vitro binding of midazolam. In vivo this is manifest as an increase in the rapidity of action of the benzodiazepines. Probenecid pretreatment will also cause a decrease in the onset time of midazolam. However, this is not due to altered plasma protein binding of the sedative.

Adolescent↗
PubMed1984

The influence of H2 receptor antagonists on the plasma concentrations of midazolam and temazepam.

This study shows that 1 day's treatment with cimetidine or ranitidine causes a raised relative systemic availability of orally administered midazolam (p less than 0.01), but pretreatment with a common emulsion antacid does not alter bioavailability. Temazepam bioavailability after oral administration is unchanged after either H2 receptor antagonist, or after the emulsion antacid. The difference in the systemic availability of the two benzodiazepines following pretreatment with either cimetidine or ranitidine may be explained by inhibition of the mixed function oxidase system in the liver. Drugs with a relatively high liver extraction ratio, such as midazolam, are likely to be affected to a greater extent than those with a low extraction ratio, such as temazepam. The clinical relevance of these findings is yet to be determined.

Administration, Oral↗
PubMed1983

Some considerations on the estimation of steady state apparent volume of distribution and the relationships between volume terms.

Application of statistical moment theory to four methods which do not involve detailed compartmental analysis for the determination of Vss shows them to be equal. Assuming drug to be eliminated exclusively from the central compartment results in the minimum value of Vss being determined. A method for determining the maximum possible value of Vss is shown which uses AUC, dose (iv), and the exponents which describe the plasma-concentration time curve. The relationships between the volume terms Vextrap, Varea and Vss are discussed in terms of moment theory.

Humans↗
PubMed1983

Estimation of absolute bioavailability assuming steady state apparent volume of distribution remains constant.

The limitations of using estimates of extent of bioavailability (F) based on the assumption that either clearance (CL) or Varea remain, constant are discussed in relation to the situation where CL changes between doses. When estimates of F assume CL to remain constant, the extent of the error is the same for all drugs where the percentage change in CL is the same. Assuming Varea to remain constant, the error in F will vary between drugs for similar percentage changes in CL and is related to the extent to which the kinetics of the disposition process deviate from a one compartment body model. A noncompartmental method is described where, provided the reference dose is given intravenously, F can be estimated based on the assumption that Vss remains constant between doses. This method is more accurate than those based on the assumption that either CL or Varea remain, constant when CL changes between doses, but is subject to error when the terminal log-linear slope of Cp vs. time better reflects the process of absorption rather than elimination.

Biological Availability↗