Search PubMed⌕ Search

Biomedical subjects

L J Lesko

Publications and source records attributed to L J Lesko.

80 records · Page 5Linked to original sources
PubMedDate not supplied

Steady state relative bioavailability and pharmacokinetics of oral propranolol in black and white North Americans.

The steady state bioavailability and pharmacokinetics of propranolol over two consecutive dosing intervals were investigated in 18 black and 10 white normal volunteers following the administration of 20 mg of a test and reference oral dosage form, respectively, every 6 h. There were no differences (p greater than 0.05) between dosage forms in the mean (n = 28) area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax) or time to Cmax (tmax) for propranolol or its active metabolite, 4-hydroxypropranolol. However, as a group blacks had lower plasma concentrations of propranolol during the second dosing interval (AUC-2 and Cmax-2, respectively) were significantly (p less than 0.05) lower in blacks, but there were no ethnic differences (p greater than 0.05) in tmax. The mean AUC and Cmax for the 4-hydroxylated metabolite during both dosing intervals were significantly (p less than 0.05) lower in blacks. Mean oral clearances of propranolol, assuming complete absorption, (range: 42.1-54.5 ml min-1 kg-1) were similar (p greater than 0.05) in each racial group. There were no substantial changes in heart rate or blood pressure in blacks or whites following propranolol administration. These data suggest that for oral propranolol, blacks have different absorption and disposition characteristics than whites.

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of nifedipine in patients at steady state.

The pharmacokinetics and associated pharmacodynamics of nifedipine were studied at steady state in 12 patients with angina pectoris who were receiving nifedipine 10-40 mg tid. After dosing, serum nifedipine concentrations rose rapidly and decayed in a log-linear fashion. The mean (+/- SEM) maximum serum concentration (Cmax) after dose normalization, and the time to Cmax (tmax) were 115 +/- 7 ng/mL and 0.72 +/- 0.13 hr, respectively. The mean area under the plasma concentration-time curve per 10-mg dose was 304 +/- 34 hr-ng/mL. The average elimination rate constant was 0.205 +/- 0.016 hr, and the harmonic mean elimination half-life was 3.4 hr (range, 2.5-4.9 hr). Heart rate increased (5-6 beats/min, P less than .05) from baseline for up to one hour after dose, while mean diastolic blood pressure decreased (6-15 mm Hg, P less than .05) for up to four hours. Cardiac output was increased (1.1-2.8 L/min, P less than .05), and calculated total systemic resistance (3.8-6.3 mm Hg/L/min, P less than .05) was decreased for the entire dosing interval after nifedipine dosing. Hysteresis plots for heart rate and mean diastolic blood pressure showed a time lag between changes in serum nifedipine concentrations and heart rate, but not between serum nifedipine concentrations and blood pressure. Changes in cardiac output did not correlate with serum nifedipine concentrations. The steady-state kinetic and dynamic parameter values in patients with angina pectoris in this study were similar to those found in healthy volunteers or hypertensive patients after acute nifedipine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

Dose-dependent elimination kinetics of theophylline.

There are an increasing number of clinical and experimental studies appearing in the literature suggesting that the elimination kinetics of theophylline may be dose-dependent in man. Evidence of nonlinearity includes observations that steady-state serum theophylline concentrations may increase disproportionately with increases in dose and that the elimination half-life of theophylline after multiple doses is longer than after single doses. Theophylline is apparently eliminated by parallel Michaelis-Menten and first-order kinetics. Although no specific studies of theophylline metabolism have been carried out to determine the causes of nonlinearity, it would appear that 1-demethylation of theophylline is a potentially saturable metabolic pathway. Dietary methylxanthines or their metabolites may influence the rate of elimination of theophylline and contribute to the causes of nonlinearity. Until the elimination kinetics of theophylline have been studied in more detail as a function of dose, it would seem prudent to increase doses of theophylline cautiously to minimise the risks of adverse side effects which might be associated with unexpected accumulation of theophylline.

Animals↗
PubMedDate not supplied

Pharmacokinetic interaction between theophylline and chloramphenicol in rats.

The effects of chloramphenicol, a potent enzyme inhibitor, on the pharmacokinetics of theophylline were investigated in Sprague-Dawley rats. Chloramphenicol treatment, 75 mg/day intravenously for 3 days, significantly (p less than 0.05) decreased the plasma clearance of theophylline by 31% with no apparent effects on the volume of distribution (0.97 liter/kg). The elimination half-life in chloramphenicol treated rats (N = 6) was 4.8 hr, significantly (p less than 0.05) longer than the corresponding half-life, 3.4 hr, in control rats (N = 6). It appears that chloramphenicol has a marked inhibitory effect on the activity of the cytochrome P-450-dependent mixed function oxidase liver microsome system responsible for the oxidation and demethylation of theophylline.

Animals↗