Pharmacokinetic interaction of megestrol acetate with zidovudine in human immunodeficiency virus-infected patients.

This nonrandomized, two-period crossover study was performed to assess whether concomitant administration of megestrol acetate influences the steady-state pharmacokinetics of zidovudine and its inactive 5'-O-glucuronide metabolite. Twelve HIV-positive, asymptomatic male volunteers received a 100-mg oral capsule dose of zidovudine at least 30 min before meals five times a day at 0700, 1100, 1500, 1900, and 2300 h on study days 1 to 3 and a single 100-mg dose at 0700 h on day 4. On days 5 to 17, 800 mg of megestrol acetate, as a 40-mg/ml aqueous suspension, was administered orally immediately before the 0700 h dose of zidovudine.

Single-dose and steady-state pharmacokinetics of fosinopril and fosinoprilat in patients with hepatic impairment.

The single-dose and steady-state pharmacokinetics of the angiotensin-converting enzyme (ACE) inhibitor fosinopril and its active diacid, fosinoprilat, were evaluated in 6 healthy volunteers and 12 patients with alcoholic cirrhosis. Fosinopril was administered at a dosage of 10 mg once daily for 14 days. Results in the two groups were similar, with no evidence of accumulation of fosinoprilat in hepatically impaired patients.

A study of pharmacokinetic interaction between buspirone and alprazolam at steady state.

The steady-state pharmacokinetic interaction between buspirone and alprazolam was evaluated in a parallel study with two groups of 12 male volunteers each. On days 1 to 7, group I subjects received a 1-mg alprazolam tablet every 8 hours (q8h) (TRT 1) and group II subjects received 2 x 5-mg buspirone tablets q8h (TRT 2). On days 8 through 14, all subjects received a combination of 1-mg alprazolam and 2 x 5-mg buspirone tablets q8h (TRT 3).

The emergence of cardiac surgery. I. Personal recollections of the 1940s and 1950s.

"Personal recollections" is given temporal torture back to the pessimism of Aristotle, Bilroth, and Paget. The delightful triumph of the "doers" in Rehn's suture of a stab wound and Souttar's intracardiac mitral valve manipulations is saluted. The brave but disappointing adventures of Doyan, Duval, Tuffier, Carrel, Graham, Beck, and Cutler are noted.

Warfarin-induced alopecia.

Earlier reports of the association between oral anticoagulation and alopecia describe a high incidence of this complication (42 to 78 percent). However, judged by its extreme rarity in a survey of eight experienced, busy academic dermatologists in Boston, this association is not common, nor is the assumption that the alopecia tends to occur soon after the administration of warfarin necessarily true. Nevertheless, alopecia persists in the face of continued warfarin administration; the time required for hair to regrow after discontinuation of the drug may be too long to be practical if continued anticoagulation is necessary; the effect of oral substitutes for warfarin is unknown; and alopecia may recur if the patient is rechallenged with warfarin.

Pharmacokinetics of mitomycin C in dogs: application of a high-performance liquid chromatographic assay.

A normal-phase high-performance liquid chromatographic (HPLC) assay was developed for the determination of mitomycin C in plasma and urine. The method involves extraction of mitomycin C from plasma or urine into ethyl acetate-2-propanol-chloroform (70:15:15) with UV detection at 365 nm. Quantitation was performed with an internal standard (porfiromycin) by the peak height ratio method.

Evaluation of the bioavailability of sarpicillin, the methoxymethyl ester of hetacillin, in humans.

The relative bioavailability of sarpicillin (the methoxymethyl ester of hetacillin) from three different oral dosage forms was compared in humans employing a three-way crossover study design. Each unit dose contained 250 mg of sarpicillin in terms of anhydrous ampicillin activity. The comparative bioavailability of a tablet containing added buffer, a liquid-filled capsule, and a standard powder-filled capsule was determined.

Correlates of angina pectoris among men awaiting coronary by-pass surgery.

Biomedical, behavioral, and psychological correlates of angina pectoris were identified in 204 men awaiting coronary artery by-pass graft surgery. Angina was rated by use of a precoded series of interview questions. Four circumstances of anginal symptoms were investigated: exertional, emotional, post-prandial, and while resting or sleeping.

Pharmacokinetics of intramuscular ceforanide in infants, children, and adolescents.

We studied the pharmacokinetics of intramuscular ceforanide in 46 infants, children, and adolescents, ranging in age from 1 month to 17 years. After the subjects were given 20-mg doses of ceforanide per kg, the mean peak plasma concentration was 56.3 microgram/ml (range, 27.

Surgeons look at medical instrumentation in the twentieth century: progress, problems, and prospects. Part I.

To obtain expert opinions as to the great medical breakthroughs of the twentieth century and of the decade of the seventies, personal letters were sent to 683 leading surgeons of the United States and Canada. Letters lost or returned by the post office reduced the survey to 487. There were some 320 immediate responses (66%).

Human pharmacokinetics and disposition of sarmoxicillin, a lipophilic amoxicillin prodrug.

Sarmoxicillin, an amoxicillin prodrug, is the methoxymethyl ester of hetamoxicillin. Esterification converted amoxicillin from an amphoteric to a cationic compound and resulted in a 30- to 600-fold increase in lipid partitioning. Oral absorption studies in normal subjects demonstrated that sarmoxicillin was only partially hydrolyzed by nonenzymatic and gut or hepatic first-pass metabolism and that significant quantities of intact ester appeared in the systemic circulation.

Comparative tissue distribution of ceforanide, cefazolin, and cefamandole in rats.

The comparative tissue distribution of ceforanide, cefazolin, and cefamandole was determined in rats after subcutaneous doses of 100 mg/kg. Ceforanide had the longest plasma half-life, 0.9 h, versus 0.

Effect of dosing volume on intramuscular absorption rate of aminoglycosides.

The Loo-Riegelman method was applied to serum amikacin level data after intravenous and intramuscular administration. Intramuscular amikacin absorption can be described by first-order kinetics, but the absorption rate constant decreased from 1.95 hr-1 at a 125-mg dose to 1.

Preliminary studies of the pharmacokinetics of talisomycin in the rhesus monkey.

The single dose intravenous pharmacokinetics of talisomycin (3 mg/M2) and bleomycin (18 U/M2) were determined in the rhesus monkey at non-nephrotoxic doses. Serum concentrations were analyzed by radioimmunoassay procedures. The tissue distribution of talisomycin was significantly higher and the elimination slower than bleomycin.

Bioavailability and metabolism of potassium phosphanilate in laboratory animals and humans.

Phosphanilic acid is an antibacterial agent with a mode of action and antibacterial spectrum similar to those of sulfamethoxazole, with the exception that it has potent antipseudomonal activity. Bioavailability studies in rats (50, 300, and 600 mg/kg, oral and subcutaneous), dogs (50, 150, and 450 mg/kg, oral and intravenous infusion), and humans (400 and 800 mg, oral) showed that the extent of oral absorption of potassium phosphanilate was low. The bioavailability, calculated by comparing the oral values for area under the plasma concentration curve with those for the respective parenteral doses, was 10% for rats and 45 (50 and 150 mg/kg) and 19% (450 mg/kg) for dogs.