1 The influence of a meal containing cooked meat (225 g) on creatinine plasma concentration, creatinine urinary excretion and creatinine clearance was determined in six healthy male subjects. 2 The meat meal produced an average 52% increase in creatinine plasma concentration within 1.5 to 3.5 h after ingestion. The 24 h area under the creatinine plasma concentrationtime curve increased by about 19%. Urinary creatinine excretion during 24 h increased by an average of 13%. Creatinine clearance was not altered in response to the meal of cooked meat.

The pharmacokinetics and bioavailability of phenobarbital were examined in six healthy adult subjects after a 2.6 mg/kg intravenous and a 2.9 mg/kg oral dose. Serum concentrations of phenobarbital were followed by means of a high pressure liquid chromatographic assay for 21 days after drug administration. After the intravenous dose, the mean distribution half-life was 0.18 hour and the mean elimination half-life was 5.8 days. Mean total body clearance and mean renal clearance were 3.0 ml/hr/kg and 0.8 ml/hr/kg, respectively. The apparent volume of distribution was 0.60 liter/kg. After administration of phenobarbital tablets, the maximum phenobarbital serum concentration was 5.5 mg/liter at 2.3 hours after the dose. Adjusted absolute availability of phenobarbital from the tablets studied was 94.9 per cent (range 81-111.9 per cent). The elimination half-life averaged 5.1 days for the oral dose. There was no evidence of autoinduction of phenobarbital elimination over the study period.

The effects of beta adrenergic blockade on theophylline elimination were studied in nine nofmal subjects. Oral propranolol, 40 mg every 6 hr, induced a fall in theophylline clearance from 0.0464 +/- 0.0294 +/- 0.0129 l/kg/hr (p < 0.001). Oral metoprolol, 50 mg every 6 hr, did not reduce theophylline clearance in the group as a whole but had reducing effect intermediate to that of propranolol on theophylline clearance in some smokers whose theophylline clearance was high initially. Beta adrenergic blockade may reduce theophylline clearance, particularly in subjects whose theophylline metabolism has been induced by cigarette smoking.

The effects of administration of metoprolol and propranolol on lidocaine elimination were studied in six healthy young men who did not smoke. Each received three single intravenous doses of lidocaine (2.5 to 3.0 mg/kg injected over 10 min): one alone, one after 1 day pretreatment with propranolol (40 mg orally every 6 hr), and one after 1 day pretreatment with metoprolol (50 mg orally every 6 hr). Lidocaine clearance was 0.88 +/- 0.28 l X hr-1 X kg-1 before beta blockade, 0.61 +/- 0.20 l X hr-1 X kg-1 during metoprolol dosing, and 0.47 +/- 0.16 l X hr-1 X kg-1 during propranolol dosing. There was no correlation between the change in lidocaine elimination and the steady-state concentrations of metoprolol or propranolol, nor between the change in lidocaine clearance and the change in resting heart rate produced by either beta blocker. Metoprolol and propranolol reduce lidocaine elimination significantly.