Practolol, a recent and more selective beta-adrenergic receptor blocking drug, was given orally as a single dose of 200 mg to seven healthy volunteers and to six patients suffering from severe renal impairment and submitted to the long-term hemodialysis program. The plasma drug decay was markedly slowed and the plasma half-life was prolonged sixfold in the uremic patients in comparison to healthy volunteers. Hemodialysis (8 hours) starting 48 hours after drug intake lowered plasma practolol significantly but transiently. The shorter half-life during hemodialysis and the detection of equally high values of practolol in the ultrafiltrates as in the plasma demonstrate that this drug is readily removable from the plasma. However, the ascending slope of the plasma drug concentration curve which appeared following hemodialysis is suggestive of an incomplete drug removal from the body.

Adult↗

PubMedDate not supplied

Pharmacokinetic study of cefazaflur compared to cephalothin and cefazolin.

A single 1-Gm dose of cefazaflur, a new semisynthetic cephalosporin derivative, was compared in a crossover study to the same dose of cephalothin and cefazolin by intramuscular injection in seven healthy volunteers. Serum concentrations were measured at several time intervals during 6 hours following each administration. The mean peak serum levels obtained after 30 minutes were 25.2, 17.2, and 62.3 mug/ml, respectively, for cefazaflur, cephalothin, and cefazolin. In each of the seven subjects, serum concentrations were higher at each sampling time with cefazolin than with the other two cephalosporins. The percentage of total administered dose recovered in urine in a microbiologically active form for the 0-24-hour collection was, respectively, 92.7, 59.2, and 94.9 per cent with cefazaflur, cephalothin, and cefazolin, the largest part being excreted during the first 6 hours. Neither drug appeared to have any pronounced effect on various laboratory tests. Local reactions at the site of intramuscular injection were minor with cefazaflur and cefazolin, but were more pronounced with cephalothin.

Adult↗

PubMedDate not supplied

Effects of simvastatin and pravastatin on 6 beta-hydroxycortisol excretion, a potential marker of cytochrome P-450 3A.

The influence of two inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, simvastatin and pravastatin, on the level of urinary 6 beta-hydroxycortisol/17-hydroxycorticosteroids (6 beta-OHC/17-OHCS) ratio was determined in two groups of normolipidemic Caucasian subjects (n = 18 and n = 14, respectively). The 6 beta-OHC/17-OHCS ratio increased significantly after simvastatin administration (20 mg day-1 for 17 days) (P = 0.0125) whereas no modification was observed after pravastatin administration (20 mg day-1 during 17 days). As the level of 6 beta-OHC/17-OHCS ratio is a function of cytochrome P-450 3A activity, these results suggest that in Caucasian subjects, simvastatin but not pravastatin could be a weak inducer of cytochrome P-450 3A. This contrasting effect could be related to the major pharmacological differences existing between these two drugs.

17-Hydroxycorticosteroids↗

PubMedDate not supplied

Absolute bioavailability of mianserin tablets and solution in healthy humans.

A pharmacokinetic study with mianserin . HCl was performed in six healthy male subjects. The subjects were treated on different occasions intravenously with a constant-rate infusion of 5 mg mianserin. HCl in 1 h, orally with a single dose of 60 mg as two tablets of 30 mg each and with 60 mg as an oral solution. The wash-out period between treatments was 1 month. Blood samples were taken at predetermined times over a period of 120 h following dosing. The mianserin concentration in the plasma samples was determined and the results were pharmacokinetically analyzed. The intravenous data could be adequately described by a 3-compartment model and the oral data by a 2-compartment model, both with first-order transfer and elimination rate constants. The mean plasma clearance of mianserin was found to be 19 +/- 2 l h-1 (mean +/- SEM), the kinetic volume of distribution 444 +/- 250 l, the steady-state volume of distribution 242 +/- 171 l and the elimination half-life 33 +/- 5 h. The absolute bioavailability in terms of extent of absorption was 22 +/- 3% for the solution and 20 +/- 3% for the tablets. The mean peak level for the solution was 79 +/- 11 ng X ml-1 and for the tablets 54 +/- 5 ng X ml-1; mean peak time for the solution was 1.1 +/- 0.2 h and for the tablets 1.4 +/- 0.2 h. The mean absorption half-life for the solution was 0.43 +/- 0.13 h and for the tablets 0.39 +/- 0.11 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

The metabolic fate of 14C or 35S labelled tiadenol in rabbit after i.v. and oral administration.

Tiadenol is a hypocholesterolemic drug that inhibits the early steps of cholesterol synthesis. No pharmacokinetic data have thus far been reported for man and few for animals. We investigated the pharmacokinetics, biotransformation and distribution of two differently labelled tiadenol molecules (14C and 35S) in the rabbit. Following a short protocol (up to 8 h), a regular decrease of the plasma radioactivity was observed after i.v. route for 4 or 5 h and plateaued thereafter. Most of the radioactivity was found in the urine, the lungs and the liver with low levels in bile and feces. By oral route, the plasma radioactivity increased regularly and decayed for a short period. Thereafter, a second increase was observed. Drug and metabolites accumulated in the kidneys and in the liver but most of the radioactive compounds were recovered from the urine. From results obtained with a longer protocol (4 days in a metabolic cage), it could be extrapolated that 10 to 15 days are necessary to completely clear the drug. Tiadenol was extensively metabolized with a wide tissue distribution. The main metabolites identified were oxidation products (free or conjugated). No statistically significant differences in biotransformation were found between the two differently labelled tiadenol molecules.

Administration, Oral↗

PubMedDate not supplied

Oral bioavailability of nizatidine and ranitidine concurrently administered with antacid.

This four-way crossover open-label study on eight healthy subjects was designed to investigate the effect on bioavailability of orally administered nizatidine given concurrently with an antacid (magnesium hydroxide-aluminium hydroxide mixture). Ranitidine was used as a comparison. Subjects were hospitalized overnight for each drug application which was given as a single dose [nizatidine or ranitidine (300 mg) or antacid (20 ml) of a neutralizing capacity of 50 mmol hydrochloric acid]. Plasma nizatidine or ranitidine concentrations were measured by high performance liquid chromatography. No statistically significant difference occurred in the kinetic profile of nizatidine after antacid administration although it took longer to reach maximum concentration in plasma. The area under the concentration-time curve was also reduced (by less than 10%) and there was a longer lag between administration and absorption. Bioequivalence (Westlake test) for ranitidine in the presence or absence of antacid was confirmed (difference less than 12%). For nizatidine, with or without antacid, the value of the Westlake test was just above the limit for bioequivalence (21.4%), whereas the Student's t-test for related means (one-tailed distribution) gave P = 0.045. There was no clinically relevant nizatidine-antacid interaction at the doses used in this study.

Adult↗

PubMedDate not supplied

Oral bioavailability of ampicillin and amoxycillin alone and bound in fixed proportions to sulbactam and clavulanic acid.

Oral bioavailability of ampicillin when bound to sulbactam (sultamicillin) compared with ampicillin alone and that of amoxycillin with a ligand of clavulanic acid versus amoxycillin alone were assessed in 16 healthy subjects using an open label, multiple crossover study. After a single administration of the drugs, the bioavailability of ampicillin released from sultamicillin was more than twice (2.17) that of ampicillin administered alone, whereas that of amoxycillin was increased by a factor of 1.64 by the presence of clavulanic acid. Higher peak concentrations and areas under the curves, along with shorter lag times, were observed in both cases. The increased oral bioavailability of these aminopenicillins when associated with a beta-lactamase inhibitor was well demonstrated in this study, the bioavailability of ampicillin being more enhanced by sulbactam than that of amoxycillin by clavulanic acid.

Administration, Oral↗

PubMedDate not supplied

[beta-adrenergic drugs on the treatment of bronchial asthma. Use and dangers (author's translation)].

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Aerosols↗

PubMedDate not supplied

Effect of oral contraceptive use on the incidence of impaired glucose tolerance and diabetes mellitus.

Combined estrogen-progestin high-dose oral contraceptives increase the risk of impaired glucose tolerance which is estimated at approximately 12% of oral contraceptive current users. Glucose tolerance is adversely affected by the chemical structure of the progestins contained in oral contraceptives such as estrane (norethindrone, ethynodiol) and particularly gonane (norgestrel). The women at high risk to develop an impaired glucose tolerance on high-dose, oral contraceptives are those with previous gestational diabetes, with a positive family history of diabetes mellitus in a first-degree relative, or who are obese or older. Low-dose oral contraceptives with a reduced content of estrogen and progestogen such as levonorgestrel or desogestrel as well as the triphasic oral contraceptives containing a low daily dose of levonorgestrel or gestodene, are associated with a significantly lower risk of impaired glucose tolerance, even in women with previous gestational diabetes. Noteworthy however is the ability of low-dose progestogen containing oral contraceptives, such as low dose gonane or estrane oral contraceptives, to induce glucose intolerance by increasing the plasma insulin response to oral glucose. Impaired glucose tolerance is often reversible within 6 months of discontinuing oral contraceptives, except for oral contraceptive users with previous gestational diabetes. Development of diabetes mellitus in high-dose oral contraceptive users is rare.

Contraceptives, Oral, Combined↗