Twelve healthy male volunteers were treated with 1200 mg/day cimetidine, 300 mg/day ranitidine, or no H2-receptor antagonist (control) for seven days in a sequence determined by Latin-square design. Each treatment period was separated by a seven-day washout. On the third day of each treatment period, 80 mg propranolol every 12 hours for nine doses was initiated. Whole blood concentrations of propranolol and 4-hydroxypropranolol were measured at 12 time points during the 12-hour period following administration of the last propranolol dose. Heart rate was measured before each blood sample was withdrawn. Cimetidine treatment was associated with a 47 per cent increase in the area under the propranolol concentration-time curve and a 17 per cent increase in elimination half-life of propranolol. Ranitidine had no significant effect on the concentration-time profile of propranolol. There were no significant differences in the 4-hydroxypropranolol pharmacokinetic parameters during any of the treatments. There was, however, a significant decrease in the average 4-hydroxypropranolol-to-propranolol steady-state concentration ratio during the cimetidine treatment. There was no significant difference in heart rate between any of the treatments. The elevation of propranolol concentrations during cimetidine treatment is likely due to metabolic inhibition by cimetidine.

Adult↗

PubMedDate not supplied

Lack of effect of histamine H2-receptor antagonists on indocyanine green disposition measured by two methods.

Eleven healthy male volunteers were treated according to a randomized, crossover design with ranitidine (300 mg/day), cimetidine (1200 mg/day), or nothing for 48 hours. Ninety minutes after the 48-hour dose, each volunteer was given 0.5 mg/kg indocyanine green by iv bolus. Indocyanine green plasma concentrations were measured by the traditional spectrophotometric method at 800 nm and by HPLC simultaneously monitored at 214 and 656 nm. Neither histamine H2-receptor antagonist altered the disposition of indocyanine green. The mean (+/- S.D.) plasma clearance by the spectrophotometric method was 7.48 +/- 2.07 (control), 7.15 +/- 3.07 (ranitidine), and 6.88 +/- 1.35 ml/min/kg (cimetidine). The power to detect a 20 per cent change is 0.87. The spectrophotometric method generally produced a biexponential plasma concentration decay, whereas the HPLC method resulted in a monoexponential decay. Analysis of the 5- to 15-minute data by the conventional technique showed that although indocyanine green total plasma clearance was not significantly different for the two methods (P greater than 0.10), the volume of distribution was significantly greater (P less than 0.001) and the elimination rate constant was significantly smaller (P less than 0.001) for the spectrophotometric than the HPLC method. Although neither ranitidine nor cimetidine chronic administration alters indocyanine green disposition by either method, the absolute values of the pharmacokinetic parameters are dependent upon the analytical technique employed.

Adult↗

PubMedDate not supplied

Inhibition of tolbutamide elimination by cimetidine but not ranitidine.

This study was designed to compare the effects of equivalent therapeutic doses of two H2 antagonists, cimetidine and ranitidine, on tolbutamide pharmacokinetics. Twelve healthy men were given a 1-g oral dose of tolbutamide on three occasions. Subjects were randomly assigned to three treatments in a crossover fashion: cimetidine 1,200 mg/d, ranitidine 300 mg/d, and placebo. Cimetidine significantly increased the tolbutamide area under the plasma concentration-time curve by 20% (range, -5% to 42%), increased the elimination half-life by 17%, and decreased the carboxytolbutamide:tolbutamide plasma ratio from 0.042 to 0.036. Ranitidine did not significantly alter tolbutamide pharmacokinetics.

Adult↗

PubMedDate not supplied

Estimating environmental exposures to sulfur dioxide from multiple industrial sources for a case-control study.

This paper first discusses how population exposures to environmental pollutants are estimated from environmental monitoring data and the problems that are encountered in estimating risk from pollutants on the basis of ecologic studies. We then present a technique of estimating individualized exposures to an atmospheric pollutant, sulfur dioxide (SO2), through atmospheric transport modeling for a case-control study. The transport model uses the quantities of SO2 released from 30 geographically identified industrial facilities and meteorological data (wind speed and direction) to predict the downwind ground-level concentrations of SO2 at geographically identified residences, receptors, of 797 study subjects. A distribution of facility SO2 emissions, uncertainties in effective stack height, and model uncertainty are incorporated to examine the uncertainty in the predicted versus ambient monitoring SO2 levels, and to generate an exposure uncertainty distribution for both the cases and controls. The transport model's accuracy is evaluated by comparing recorded ambient measurements of SO2 with the model's predicted SO2 estimates at geographically identified ambient monitoring stations.

Air Pollutants↗