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Biomedical subjects

T K Daneshmend

Publications and source records attributed to T K Daneshmend.

At least 55 records · Page 3Linked to original sources
PubMed1984

The effects of enzyme induction and enzyme inhibition on labetalol pharmacokinetics.

The oral and intravenous pharmacokinetics of labetalol were determined in five subjects before and after a 3 week course of glutethimide 500 mg/day. After glutethimide there was a significant reduction in the AUC after the oral dose of labetalol, from 40,596 +/- 11,534 (mean +/- s.e. mean) to 22,057 +/- 6,276 ng ml-1 min (2P less than 0.05), and systemic bioavailability was reduced from 30.3 +/- 2.8 to 17.0 +/- 3.5% (2P less than 0.001). There was no significant change in labetalol plasma concentration-time curve (AUC) following an intravenous dose, half-life, volume of distribution, and plasma clearance. The oral and intravenous pharmacokinetics of labetalol were determined in six subjects before and after a 3 day course of cimetidine 1.6 g/day. After cimetidine there was a significant reduction in the volume of distribution of labetalol, from 520 +/- 51 to 445 +/- 24 1 (2P less than 0.05). The AUC of labetalol after the oral dose increased by 66%, from 51,029 +/- 7,950 to 84,772 +/- 19,444 ng ml-1 min (2P = 0.06). The systemic bioavailability of labetalol increased from 25.1 +/- 2.4 to 39.0 +/- 7.6% (2P = 0.06). There was no significant change in labetalol AUC after the intravenous dose, half life, and plasma clearance. There were no significant changes in resting heart rate and supine systolic and diastolic blood pressure following labetalol plus glutethimide, or labetalol plus cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Influence of food on the pharmacokinetics of ketoconazole.

Eight healthy adults were given single oral doses of ketoconazole (200, 400, 600, and 800 mg) in the fasting state and with a standard breakfast at weekly intervals according to a balanced block design. Concentrations in serum were measured up to 32 h after the dose. Food did not reduce ketoconazole absorption or significantly alter peak ketoconazole concentrations in serum, though there was a food-related delay in achieving peak concentrations. At the 400- and 600-mg doses, food appeared to enhance absorption, but this effect was not seen at the 800-mg dose. With an increase in dose, the half-life and area under the serum concentration-time curve increased disproportionately, suggesting that the pharmacokinetics of ketoconazole may be dose dependent. Up to the 800-mg dose, the elimination of ketoconazole did not appear to be saturable. Administration of the drug with food is unlikely to be a cause of therapeutic failure.

Adult↗
PubMed1984

Effects of chronic oral cimetidine on apparent liver blood flow and hepatic microsomal enzyme activity in man.

Cimetidine 200 mg three times daily and 400 mg at night was given to 10 subjects for four weeks. Apparent liver blood flow was measured by indocyanine green clearance and microsomal enzyme activity by antipyrine clearance, before and after cimetidine. There was no reduction in indocyanine green clearance but antipyrine clearance, as expected, was significantly reduced by 15% at four weeks. Chronic cimetidine treatment does not reduce apparent liver blood flow and is therefore unlikely to be of use in the treatment of portal hypertension. The cimetidine associated hepatic enzyme inhibition appears to persist with prolonged treatment. Therefore patients on chronic cimetidine remain vulnerable to certain drug interactions.

Adult↗
PubMed1983

Multiple dose pharmacokinetics of ketoconazole and their effects on antipyrine kinetics in man.

Ketoconazole 200 mg was given twice daily for five days to eight subjects. The serum pharmacokinetics were examined with the first dose on day 1 and with the ninth dose on day 5. The serum half life of ketoconazole was 74.8 +/- 13.9 min (mean +/- S.D.) on day 1, and 155.9 +/- 32.7 min on day 5. On day 1 the area under the serum concentration time curve was 626.9 +/- 230.1 mg/l.min, and 1441 +/- 897.3 mg/l.min on day 5. Antipyrine kinetics were determined before and after the course of ketoconazole. There was no significant change in the clearance and half life of antipyrine. Ketoconazole in the doses used in this study does not appear to alter hepatic microsomal enzyme activity in man. The increased ketoconazole half life and area under the serum concentration time curve on day 5 were in part caused by food. Other mechanisms for these changes such as saturation of a tissue compartment or a change in the elimination of ketoconazole during chronic dosing, may also be responsible.

Adult↗
PubMed1982

Ketoconazole.

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Antifungal Agents↗
PubMed1982

The short term effects of propranolol, atenolol and labetalol on antipyrine kinetics in normal subjects.

1 The effects of three day courses of propranolol 40 mg three times daily, atenolol 100 mg twice daily and labetalol 100 mg three times daily on antipyrine kinetics were examined in 13 normal subjects. 2 The mean antipyrine clearance initially was 41.3 +/- 12.4 ml/min (mean +/- s.d.) and fell to 35.0 +/- 12.1 ml/min following propranolol (P less than 0.025), 34.5 +/- 9.5 ml/min following atenolol (P less than 0.01), and 35.2 +/- 8.6 ml/min following labetalol (P less than 0.05). 3 The prolongation in antipyrine half-life was significant only following atenolol. Propranolol only caused a significant reduction in the volume of distribution of antipyrine. 4 These adrenoceptor antagonists appear to decrease antipyrine clearance in normal subjects. The reduction in antipyrine clearance was similar with all three drugs and appeared to be independent of the differing lipid solubilities and pharmacological profiles of the adrenoceptor antagonists examined.

Adult↗
PubMed1982

The influence of food on the oral and intravenous pharmacokinetics of a high clearance drug: a study with labetalol.

1 The effects of food on the pharmacokinetics of orally and intravenously administered labetalol were assessed in six healthy volunteers. 2 Food caused a 38% increase in the mean systemic bioavailability of labetalol: from 0.26 +/- 0.03 (mean +/- s.e. mean) to 0.36 +/- 0.05 (P less than 0.05). 3 Food caused 20% increases in the volume of distribution of labetalol: (from 567 +/- 63 to 685 +/- 76) and in plasma clearance (from 1923 +/- 417 to 2344 +/- 566 ml/min. These changes did not reach statistical significance. Food did not alter the plasma half-life of labetalol after oral or intravenous dosing. 4 Food appears to increase labetalol bioavailability by decreasing its first pass metabolism. It is suggested that this change results from transient alteration of hepatic blood flow. The drug should therefore be taken at a standard time in relation to meals to minimise intraindividual variation in bioavailability.

Administration, Oral↗
PubMed1982

Disposition of oral metronidazole in hepatic cirrhosis and in hepatosplenic schistosomiasis.

The pharmacokinetics of metronidazole 500 mg orally were determined in patients with hepatosplenic schistosomiasis and normal controls in the Sudan, and in cirrhotics and normal controls in Bristol. Plasma metronidazole levels were above the minimum inhibitory concentration of most susceptible anaerobic bacteria for four to six hours post-dose in all groups. Liver disease did not markedly influence the disposition of single oral doses of metronidazole. Cirrhotics showed some prolongation of metronidazole half-life, and somewhat greater metronidazole concentrations 24 hours after the dose. Concentrations of the oxidative metabolite of metronidazole were lower in Sudanese patients and normal controls than in normal British subjects. In chronic liver disease adjustment of metronidazole dosage is probably not required provided renal function is unimpaired.

Administration, Oral↗
PubMed1982

Effects of cirrhosis and ageing on the elimination and bioavailability of ranitidine.

The plasma concentrations of ranitidine after oral and intravenous administration have been measured in 10 healthy young adults, nine cirrhotic patients, and eight healthy elderly people. In the first of these bioavailability was 51 +/- 4% and half life 161 +/- 11 minutes after oral and 124 +/- 5 minutes after intravenous administration. In the cirrhotics bioavailability was increased to 70 +/- 7%, clearance was reduced, and there was a modest increase in half life. In the elderly bioavailability was similar to that in young adults, clearance was markedly reduced, and half life was prolonged to 241 +/- 7 minutes after oral and 194 +/- 11 minutes after intravenous administration. It is predicted that blood levels in cirrhotics and the elderly would be 50 to 60% higher than in healthy young adults after repeated oral administration of similar doses.

Administration, Oral↗
PubMed1981

Dose-response studies of indenolol, a beta adrenoceptor blocker.

Two studies were conducted on indenolol, a new beta-adrenoceptor blocker. In the first, nine healthy men received indenolol 40, 80, 160, and 320 mg and placebo orally. Two hours later a standard exercise test was performed, and systolic blood pressure, heart rate, and peak expiratory flow rate were recorded. Indenolol induced attenuation of exercise-induced rise in systolic blood pressure and tachycardia. In the second study, seven healthy men received indenolol 40, 80, 160, and 320 mg and propranolol 40, 80, 160, and 320 mg in randomized order. Dose-response curves for both drugs revealed that maximum attenuation of exercise tachycardia and systolic blood pressure were in the same range but suggested that indenolol induced a greater response in the lower doses. Neither drug had any effect on the exercise-induced rise in peak expiratory flow rate. Indenolol was well tolerated.

Adrenergic beta-Antagonists↗