Pharmacokinetics and bioavailability of a new formulation of teicoplanin following intravenous and intramuscular administration to humans.

Pharmacokinetics, bioavailability, and local tolerance (at the site of intramuscular administration) of a new formulation of teicoplanin (400 mg/3 mL) were investigated in 24 normal, healthy, male volunteers. A single dose of 6 mg/kg was administered intravenously and intramuscularly using a randomized crossover design. Volunteers and investigator were blinded as to the route of administration; placebo was administered by the other route. Blood and urine samples were collected for 21 days and were analyzed for microbiological activity. The median (range) pharmacokinetic parameters of teicoplanin following single-dose iv administration were as follows: steady-state volume of distribution of 1.6 (1.2-2.8) L/kg; total clearance of 10.2 (8.6-15.1) mL/h/kg; renal clearance of 10.0 (7.9-13.8) mL/h/kg; and terminal disposition half-life of 168 (111-278) h. Following single-dose im administration, significantly more subjects complained of pain following administration of teicoplanin (58%) compared with placebo (4%). Teicoplanin was completely absorbed with a median (range) peak serum concentration of 12.3 (6.6-37.5) micrograms/mL occurring at a median (range) time of 4.1 (0.7-6.1) h. Since the 90% confidence interval for the ratio of areas under the serum concentration-time curve falls within the range of 80 to 120%, the extent of systemic absorption of teicoplanin following im administration is equivalent to that following iv administration.

Effects of medroxalol on renal function and the renin-angiotensin-aldosterone axis.

Ten subjects with hypertension received medroxalol, which blocks both alpha- and beta-adrenergic receptors, has intrinsic sympathomimetic beta 2-agonist properties and is a direct vasodilator. Renal function tests consisting of inulin clearance and p-amino hippuric acid (PAH) clearance, plasma renin activity (PRA) in recumbent and upright postures, and aldosterone excretion rate were performed. After intravenous medroxalol, inulin clearance and PAH clearance rose, renal vascular resistance fell, recumbent PRA was unchanged, and the rise in PRA with upright posture was blunted. After 1 mo on oral medroxalol, blood pressure was controlled while inulin clearance, PAH clearance, and renal vascular resistance were unchanged. The rise in PRA with upright posture remained blunted. Urinary aldosterone excretion was unchanged after 1 mo on medroxalol.

Anticholinergic activity of two tricyclic antidepressants.

Using a double-blind crossover Latin square design, the authors evaluated the peripheral anticholinergic and central nervous system effects of three dose levels of two tricyclic antidepressants in female volunteers. Results showed that 5 hours after drug administration, desipramine (50 and 100 mg) caused significantly less reduction in salivation than did amitriptyline. Amitriptyline produced more sedation (Clyde Mood Scale) and a greater number of subjective complaints than did desipramine. These results are consistent with anticholinergic profiles from animal experiments and suggest that clinically meaningful differences may exist among tricyclic antidepressants.

Ohio drinking water source and cancer rates.

The 88 counties of Ohio were classified as either ground water or surface water counties based on the source of the drinking water used by a majority of the county residents included in the 1963 U.S. Public Health Service Inventory of Municipal Water Facilities. Average cancer mortality rates for surface and ground water counties were compared using analysis of covariance. Mortality rates for stomach, bladder, and all malignant neoplasms were higher for white males in counties served by surface water supplies than in counties served by ground water supplies. Mortality rates for stomach neoplasms were higher for white females in surface water counties. These differences in mortality rates were not attributable to other factors known to be associated with cancer death rates including urbanization, median income, population size, manufacturing activity, and agriculture-forestry-fishery activity.