Effect of gugulipid on bioavailability of diltiazem and propranolol.

The effect of single oral dose of 1 gm gugulipid was studied on bioavailability of single oral dose of propranolol (40 mg) and diltiazem (60 mg) in 10 and 7 normal healthy male volunteers respectively. It was a randomised within group crossover study. Blood samples were collected at hourly intervals upto 8 hrs. Gugulipid significantly reduced (P < .01) peak plasma concentration (Cmax) and area under curve (AUC 0-8 hrs) of both the drugs in normal volunteers. Such interaction in patients receiving propanolol or diltiazem with gugulipid may lead to diminished efficacy or nonresponsiveness due to significant reduction in bioavailability.

Effect of iron deficiency anaemia and its treatment on single dose phenytoin bioavailability.

Iron deficiency is a common nutritional deficiency, which leads to structural functional and enzymatic changes in the body that may affect the pharmacokinetics of drugs. The present study in 7 normal volunteers and 8 adult male patients with iron deficiency anaemia (IDA) was done to investigate the effect of iron deficiency and its treatment with total dose iron (TDI) on the bioavailability of a single dose of phenytoin. Phenytoin bioavailability was investigated before and 3 and 28 days after TDI. The bioavailability parameters Cmax, tmax, AUC and 2 h phenytoin concentrations were not significantly different in anaemic patients as compared to normal volunteers before or after treatment, except for an increase in tmax 28 days after TDI treatment.

A study of phenobarbital and dilantin in neonatal seizures.

A total of 40 cases of neonatal convulsions of different nonmetabolic aetiological factors were studied. Patients with kernicterus were included in the study. Peak plasma phenobarbital concentrations after incremental loading doses of phenobarbital i.e. 10 mg/kg, 15 mg/kg, and 20 mg/kg were determined. Diphenylhydantoin was added if phenobarbital alone was unable to control seizures. In three patients, a combination of phenobarbital and diphenylhydantoin was used as the initial loading therapy. Increase in the loading dose of phenobarbital was associated with an increase in its peak plasma concentration. Despite increase in the plasma phenobarbital concentration beyond the 'therapeutic' levels suggested by the Western studies, doses of 15 mg/kg and 20 mg/kg of phenobarbital were unable to score over the traditional regimen of 10 mg/kg. Convulsions were controlled in 50% of the patients with any of these three regimens, irrespective of the aetiology. Convulsions were controlled in 7 out of the 9 cases where diphenylhydantoin was added, because of the failure of phenobarbital in controlling the convulsions as a single drug. Convulsions of all the three patients, in whom a combination of phenobarbital and diphenylhydantoin was used by random selection as the initial bolus, were controlled. Seizure effects were difficult to distinguish from drug effects but major side effects were not encountered despite the fluctuating drug levels in the sick neonate.

Bioinequivalence of marketed diltiazem preparations.

A bioequivalence study of three brands of regular diltiazem--Angizem (A), Dilzem (B) and Herbesser (C) has been carried out in 5 healthy, male volunteers. After a single oral dose of 60 mg of each preparation, the mean AUC (0-8 h) and Cmax of preparation B was significantly higher than of brands A and C. The tmax of A and B was significantly lower than of C. B had a higher dissolution rate in vitro (98.8% dissolved in 45 min) than A and C. Thus, there was bioinequivalence of the three brands of diltiazem, due partly to differences in dissolution and perhaps in part to a first pass effect.

Effect of iron deficiency anaemia and its treatment on the absorption and elimination of phenformin.

1. The extent of phenformin absorption and its rate of urinary excretion have been assessed in adult patients with iron deficiency anaemia, a condition which compromises gastrointestinal function. 2. Phenformin (100 mg) was administered orally to patients before treatment, three days after the start of a course of iron treatment (oral 300 mg b.d. or total intravenous iron) and at the end of 28 days, when haemoglobin was over 10 gm%. 3. No significant difference was found between mean total amounts of phenformin and 4-hydroxyphenformin excreted in urine, before treatment or after 3 or 28 days replacement therapy. It is concluded that phenformin absorption is not affected by iron deficiency. 4. In addition, iron deficiency had no significant effect on phenformin elimination half-life.

Salivary antipyrine half-life during injectable progestagen contraception.

Antipyrine pharmacokinetics were studied in 6 healthy women before and 2, 8 and 12 weeks after administering the injectable progestagen (progestin), norethisterone (norethindrone) enanthate 200mg intramuscularly. Additionally, antipyrine kinetics in 5 women who had previously used the injectable contraceptive for 8 to 14 months were compared with values obtained in 14 non-users. Antipyrine was measured in saliva using a spectrophotometric method, following an oral dose of 18 mg/kg bodyweight. In the 6 women studied prospectively the mean salivary antipyrine half-life was 14.91 +/- 1.5 hours (SEM) before administering the injection, and 13.56 +/- 0.73 at 2 weeks, 15.13 +/- 1.86 at 8 weeks and 15.21 +/- 2.46 hours at 12 weeks after the injection. The mean antipyrine half-life in the 5 long term users of injectable progestagen was 14.21 +/- 2.53 hours compared with 13.66 +/- 0.98 hours in non-users. The results of this study suggest that - in contrast to published data on combined oral contraceptives - neither short nor long term use of parenteral norethisterone enanthate in Indian women is associated with significant alterations in antipyrine clearance.

Effect of low estrogen combination oral contraceptive on metabolism of aspirin and phenylbutazone.

Plasma levels of aspirin and phenylbutazone were estimated before and during administration of low estrogen combination type oral contraceptive for two menstrual cycles in ten and seven female volunteers, respectively. Aspirin was administered at doses of 300 and 600 mg, while phenylbutazone was administered at a dose of 400 mg. Blood samples were collected at intervals of 1, 2, 4, 6, and 8 h for aspirin and 2, 4, 6, 8, 24, 48, 72, and 80 h for phenylbutazone. Plasma levels, plasma half-life (t1/2), as well as area under curve (AUC) for aspirin after use of oral contraceptive revealed lower values. Phenylbutazone levels were not affected. Repeat studies of plasma t1/2 and AUC for aspirin after discontinuation of oral contraceptive showed values similar to basal levels.

PIP: Plasma levels of aspirin and phenylbutazone were estimated before and during the administration of low estrogen combination type oral contraceptive (OC) for 2 menstrual cycles in 10 and 7 female volunteers, respectively. Aspirin was administered at doses of 300 and 600 mg.; phenylbutazone was administered at a dose of 400 mg. Blood samples were collected at intervals of 1, 2, 4, 6, and 8 hours for aspirin and 2, 4, 6, 8, 24, 48, 72, and 80 hours for phenylbutazone. Plasma levels, area under curve (AUC), and plasma half life (t1/2) of aspirin were significantly lower during OC use as compared with predrug data. This was applicable to both doses of aspirin. Plasma levels of phenylbutazone did not show significant differences. Since there were significant alterations in plasma levels of aspirin during OC use, the study was repeated after a drug free interval of 3-5 months. A rise in plasma levels and t1/2 was observed after discontinuation of OC. Tmax for aspirin was not consistently altered during OC use, but the Pmax was reduced in all cases during OC use and was found to recover in all the 7 subjects studied after discontinuation of OC. Salicylate levels in 5 women using OC for more than 2 years were similar to the levels before administration of OC.