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Biomedical subjects

R Rondanelli

Publications and source records attributed to R Rondanelli.

At least 37 records · Page 2Linked to original sources
PubMed1986

Ceftazidime in the treatment of Pseudomonas infections in intensive-care patients.

The present study was designed to define the clinical activity and pharmacokinetics of ceftazidime in Pseudomonas sp. infections. The intensive care patients included in this study were hospitalized for at least 2 weeks and have frequently received antibiotic treatment which contributed with poor host resistance to the infections with highly resistant Pseudomonas strains. Sixteen adult patients entered the study. Their age ranged from 18 to 70 years. Ceftazidime was administered in a dose of 2 g three times daily by a constant infusion over 20-30 min. Frequent clinical assessment multiple cultures and determination of renal, hepatic and bacteriological functions were performed. Bacterial cultures were obtained prior to the beginning of therapy and every 2-3 days thereafter with a follow-up period of about 1-2 weeks. Pharmacokinetics in the blood were performed. Measurements of ceftazidime were made by using HPLC. Mean peak serum concentration of ceftazidime was 58.5 micrograms/ml after administration of 2.0 g of ceftazidime and eight hours after dosing the mean plasma concentration was about 5 micrograms/ml. No accumulation of ceftazidime could be observed during the treatment period. Mean plasma half-life was 2.1 hours at the beginning and 2.2 hours at the end of therapy. The mean apparent volume distribution was 0.35 l/kg. No severe adverse effects were reported throughout the study. Ceftazidime may be effectively used as single antiinfective agent in various conditions and higher plasma concentrations are an important predictor of bacteriological and clinical response in pulmonary infections caused by Pseudomonas species.

Adolescent↗
PubMed1986

The role of psychologic stress in the genesis of lethal arrhythmias in patients with coronary artery disease.

To investigate the influence of psychologic stress on the electrophysiology of the heart and the genesis of cardiac arrhythmias, programmed ventricular stimulation was performed in 19 patients with recent uncomplicated myocardial infarction (37 +/- 10 days after the acute episode) during control conditions and during mental arithmetic. Psychological assessment showed a normal profile in all subjects. During mental stress, blood pressure increased (from 147 +/- 16/96 +/- 9 to 171 +/- 16/106 +/- 8 mmHg, P less than 0.001), and the mean ventricular refractory period decreased by 8 ms (1-3 extrastimuli P less than 0.05-0.001). Unsustained ventricular tachycardia (greater than or equal to 6 beats) was induced in 2 and 7 patients during control and during stress stimulation respectively (P less than 0.05). Ventricular fibrillation was provoked by double (1 patient) and triple (1 patient) extrastimuli during stress. In conclusion mental stress can induce measurable cardiac electrophysiological modifications in uncomplicated postinfarct patients and such modifications may favour the appearance of life-threatening arrhythmias.

Adult↗
PubMed1986

Dosing problems of gentamicin in critically ill patients.

Twenty critically ill patients with a diagnosis of possible or documented Gram-negative sepsis received gentamicin sulphate by i.v. short infusion (30 min). The same daily dose was administered in a variable frequency regimen (ten were treated by an 8 h frequency regimen and ten by a 12 h frequency regimen). Repeated measurements of gentamicin plasma levels and of serum creatinine, albumin, total proteins and haematocrit were performed simultaneously, with measurements of tubular casts, alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl-transpeptidase activity in urine. There was a considerable variation in plasma gentamicin concentrations among individuals patients and in the same patient from day to day with each dosage regimen. Despite the daily administration of at least 5 mg/kg/day of gentamicin, nephrotoxicity occurred in only one patient. The mean duration of therapy was about ten days. Although the series of patients was small, no significant difference was reported in either the 8 or 12 h dosage regimen in respect to favourable response to treatment among the patients. Probably a high peak concentration greatly exceeding the minimal inhibitory concentration (MIC) for a short duration, kills Gram-negative bacteria as effectively as a long concentration exceeding the MIC for a longer period of time. The reported half-lives and area under curve values for gentamicin in our patients varied widely even in the same patient.

Bacterial Infections↗
PubMed1986

Evaluation of the absorption from three ibuprofen formulations.

The pharmacokinetic differences between two sustained-release 300 mg (A) and 400 mg (B) formulations and a rapid-release 400 mg ibuprofen conventional sugar-coated formulation (C) were compared after a single dose. Mean peak levels of 25.1 micrograms/ml for preparation A (2 X 300 mg), 31.3 micrograms/ml for preparation B (2 X 400 mg) and 68.5 micrograms/ml for preparation C (2 X 400 mg) were reached at 5.3, 3 and 2 hours respectively, after ingestion of the drugs. The individual plasma-level time-profiles for the majority of doses suggested prolonged absorption of product A and B. The absorption from formulations A and B was significantly slower (p less than 0.001 and p less than 0.05 respectively) than that from the conventional tablets. The bioavailability of ibuprofen from sustained-release capsules, was not found to differ significantly from that of ibuprofen from conventional tablets. The relative bioavailability was very close to 100% in almost all subjects (coefficient of variation 14% and 17%). Projections of plasma concentrations upon multiple dosing were made from single dose data. The dosage interval concentration ratio which reflects both the frequency and the entry of the drug into and from the body was much lower for sustained-release formulations (A: 3.0; B: 3.7; C: 12.9).

Absorption↗
PubMed1984

Dihydroquinidine versus disopyramide: efficacy in patients with chronic stable ventricular ectopy.

Dihydroquinidine (DQ) is contained in substantial amounts in quinidine salts, but its direct antiarrhythmic action has not been studied. The efficacy of oral DQ (300 mg t. i. d.) compared to disopyramide (D) (200 mg t.i.d.) was thus investigated using a double-blind crossover placebo-controlled protocol in 12 patients, aged 13 to 67 years, with chronic stable high frequency premature ventricular beats (PVB), defined as greater than 100 PVB/h during 48-72-h control Holter monitoring. The protocol included three 72-h treatment periods: DQ, D, and placebo at random. On days 2 and 3 of each period a 24-h Holter recording was carried out; drug blood levels were determined at peak (days 2 and 3) and trough time (day 3). No significant difference in the mean PVB/h was found between control (735 +/- 400) and placebo periods (564 +/- 388), or between the two Holter recordings of each period. Compared to placebo both DQ (106 +/- 113, p less than 0.005) and D (240 +/- 263, p less than 0.05) reduced the mean PVB/h, but the decrease was significantly higher with DQ (78 versus 53%, p less than 0.02). Nine patients (75%) on DQ and 5 (42%) on D had a greater than 70% decrease in mean PVB/h; complex PVBs were abolished in 3 of 6 patients on both treatments. On day 3, DQ plasma levels were 1.31 +/- 0.44 (peak) and 0.92 +/- 0.45 (trough) mg/l; D plasma levels were 2.88 +/- 0.64 (peak) and 2.02 +/- 0.31 (trough) mg/l; no significant difference was found between day 2 and day 3 samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Pharmacokinetics and clinical efficacy of indomethacin in premature infants with patent ductus arteriosus.

Despite a considerable amount of investigation, controversy continues concerning the use of indomethacin in inducing the closure of patent ductus arteriosus. This controversy may be attributable to differences in dosage, route of administration, postnatal age at treatment and the variable pharmacokinetics of the drug in premature infants. The pharmacokinetics and clinical efficacy of i.v. administered indomethacin in five premature infants with PDA were evaluated. There was considerable intersubject variability in the half life of elimination (63.1 +/- 38 h). This variability was mainly due to clearance (0.0086 +/- 0.0069 l/h/kg) rather than to distribution volume variability (0.54 +/- 0.27 l/kg). A reduction of half life was observed after the second dose, probably due to a maturation process. A permanent closure of the ductus was obtained in two patients after the first dose and in two patients after the second dose. The side-effects observed in our infants were transient and no long-term complication was attributable to this drug.

Ductus Arteriosus, Patent↗
PubMed1983

Cefoxitin in newborn infants. A clinical and pharmacokinetic study.

Fifteen patients less than 2 months old with bacterial infections caused by pathogens known or presumed to be sensitive to cefoxitin were studied. Cefoxitin was administered as an i.v. bolus injection over 15 min, every 8 h for 6 to 12 days, to a total daily dosage of 90 mg/kg. In 14 patients cefoxitin therapy resulted in eradication of the pathogen and in recovery from clinical signs of infection. Only one patient did not respond to cefoxitin therapy. No adverse clinical or haematological effects definitely caused by cefoxitin were observed. Plasma and urine samples collected after the first dose were assayed for cefoxitin by HPLC. Pharmacokinetic data indicated larger apparent volume of distribution (0.5 1/kg), a smaller plasma clearance (0.27 1/h/kg) and a longer half-life (1.43 h) than in adults. The plasma half-life was inversely correlated (p less than 0.05) to the postnatal age of the patients. Cefoxitin may be safely used in infants with infections caused by susceptible pathogens.

Bacterial Infections↗
PubMed1983

The clinical pharmacology of drug interactions.

Preliminary evaluation of pre-established and extemporaneous combinations showed that any combination requires broad, precise, and scientifically valid documentation. Every drug has to be evaluated according to physical, chemical, and pharmacologic points of view, either individually or in combination, and above all be adapted to the individual needs of each patient. To make a realistic contribution to evaluating and devising new combinations, specialized centers should be instituted such as the Central Admixture Service of S. Matteo Hospital in Pavia.

Drug Combinations↗
PubMed1983

Bioavailability of sustained-release theophylline formulations.

Sustained-release formulations of theophylline as well as of other drugs are designed to effect a delayed but constant release of the active principle in the gastrointestinal tract, thus ensuring more prolonged blood level curves. This study was made to assess the bioavailability of two sustained-release microencapsulated formulations and one sustained-release Diffucaps formulation, in comparison with an equivalent dose of theophylline solution. As regards bioavailability, none of the three formulations differed significantly from the reference formulation. The blood levels at steady state were estimated on the basis of data obtained after a single-dose study. All three sustained release formulations showed good results after prolonged administration in terms of peaks and troughs. The time duration at which the theophylline plasma levels remain higher than 75% of the maximum steady-state levels, following 12-h dosing interval, was evaluated: for the sustained-release microencapsulated formulations this time duration reaches 100% of the dosing interval. A multiple-dose administration of the sustained-release formulations used in this study should guarantee almost complete time coverage, with blood levels sharply exceeding the minimum threshold level of the theophylline therapeutic range.

Absorption↗
PubMed1982

The bioavailability and kinetics of dihydroquinidine in patients with heart disease.

The absolute bioavailability of dihydroquinidine chloride (normal tablet and sustained-release capsule) was studied in 12 hospitalized patients with heart disease. A 300-mg dose of dihydroquinidine gluconate was administered to each patient by short intravenous infusion. After a single dose of two tablets of dihydroquinidine chloride (300 mg), the average peak concentration was 0.74 +/- 0.43 mg/l (+/- SD); following administration two capsules of the sustained-release form (500 mg dihydroquinidine chloride) the average peak concentration was 0.55 +/- 0.25 mg/l. Tmax was approximately 5 h with the dihydroquinidine tablet and 7 h with the dihydroquinidine capsule. The mean absolute bioavailability was 89 +/- 9% for the conventional tablet and 52 +/- 15% for the sustained-release capsule. After intravenous infusion of dihydroquinidine (2.63 +/- 0.29 mg/kg), the disposition of the drug is described by a two-compartment open model. The volume of distribution (Vd) was 4.67 l/kg. Distribution (t1/2 alpha = 18.63 +/- 15.2 h) and the apparent elimination half-life (t1/2 beta = 10.8 +/- 4.7 h) were longer than the corresponding values reported by Ueda et al. [1976]. These discrepancies are presumably due to the different sampling period that was extended to 24 h in our study, consequently evidencing a slower rate of elimination from 12 to 24 h. Mean total body clearance (Cl) was 0.28 +/- 0.057 l/h/kg. Urine sample collection for 48 h showed 21% of the dose was excreted unchanged. The renal clearance (Clr) was 0.062 +/- 0.018 l/h/kg.

Administration, Oral↗
PubMed1980

Clinical pharmacokinetics: the pharmacological monitoring of plasmatic levels in therapy.

Recent developments of clinical pharmacology show that in particular circumstances the determination of the plasmatic levels of drugs seems to be the best way to insure the best dosage schedules for each patient. For this and other reasons, at the Hospital Pharmacological Service a clinical pharmacokinetic laboratory was set up about two years ago. It is involved both in pharmacokinetic research with the aim of pointing out the reasons of a quantitatively or qualitatively unusual response to the drug (generally lack of therapeutic effect or untoward effects) and in finding the best practical administration route for each patient of those drugs which show a high incidence of undesirable side effects. At the moment, salicylates, quinidine, phenobarbital, phenytoin, theophylline, digoxin and gentamicin are routinely monitored. Other drugs under examination are valporic acid, methotrexate, etc. In the present paper the first results obtained are reported.

Digoxin↗
PubMed1979

Clinical-pharmacological aspects, application and effectiveness of total parenteral nutrition in surgical patients.

The term "total parenteral nutrition" (TPN) refers to the maintenance of an adequate nutritional status, normal body weight and positive nitrogen balance solely by intravenous means. It requires solutions providing calories, amino acids and other nutrients in amounts much greater than those indicated for maintenance of normal body weight. Nutrient solutions have been studied, selected and prepared in our Hospital Pharmacological Service utilizing a sterile closed system, which allows large-volume filtering, sterilizing and bottling devices. For maintenance of weight gain in adults, a basic formula is employed, which provides 1,100 Kcal/1 with pure crystalline amino acids mixed with 50% anhydrous dextrose in water in a ratio of 5.8:1 (160 Kcal:1 g nitrogen). Minerals and vitamins are added to the base solution prior to use and may be increased or decreased by simple addition or omission depending on the patient's condition. This paper is based on 192 surgical patients who received TPN and have been followed in strict cooperation between the Hospital Pharmacological Service and the Surgical Department. The patients, ranging from 23 to 79 years of age, with life threatening diseases and unable to maintain adequate nutrition by the oral route, received TPN through a central catheter inserted via subclavian puncture (146 cases) or through a surgically created internal A-V fistula (46 cases). The condition of the patients generally improved within a few days after starting TPN; and weight gain, wound healing, general improvement and a shorter period of hospitalization were observed. TPN could be efficiently combined with oncologic treatment, and a significant improvement of the patients' performance status and decrease of toxic side-effects due to chemotherapeutic agents were observed. TPN has been successfully applied also in patients with fistulas of the alimentary tract obtaining spontaneous closure and in patients with ulcerative colitis, showing its beneficial effect in allowing complete bowel rest for healing. No major complications or deaths could be attributed to TPN or to the route of administration.

Adult↗