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Biomedical subjects

Q A Mekki

Publications and source records attributed to Q A Mekki.

12 recordsLinked to original sources
PubMed1995

Pharmacokinetics of tacrolimus in liver transplant patients.

OBJECTIVE: To characterize the pharmacokinetics of the immunosuppressive agent tacrolimus (FK 506) in liver transplant patients. METHODS: Patients (n = 16) were assessed during and after 1- to 3-day intravenous infusions followed by a 2-week course of oral dose therapy. Plasma and whole blood data were fitted simultaneously with equations accounting for nonlinear drug binding by red blood cells to generate clearance (CL) and volume of distribution (V). RESULTS: The maximum blood/plasma ratio of tacrolimus was 55.5 +/- 26.8 (SD) and half-life averaged 12.1 +/- 4.7 hours. The CL and V were relatively high based on plasma concentrations (CL, 1.7 L/hr/kg; V, 30 L/kg) and low based on whole blood (CL, 54 ml/hr/kg; V, 0.9 L/kg), with moderate variability (coefficient of variation, 34% to 49%) among the patients. Correlations of plasma CL and V with maximum blood/plasma ratios (ranging from 13 to 114) were strong (r = 0.65 and r = 0.73). Blood binding affects the disposition of tacrolimus, and plasma concentrations are indirectly and inversely related to red cell binding. The oral dose data for tacrolimus yielded a brief absorption lag time (tlag, 0.39 hour), a variable first-order absorption rate constant (ka, 4.5 +/- 3.0 hr-1), and consistent bioavailability (F, 25% +/- 10%). The area under the concentration-time curve versus 12-hour minimum concentration relationships for both whole blood and plasma were nearly linear, confirming the utility of trough values for monitoring drug exposure. CONCLUSION: This study provides pharmacokinetic guidelines for the use of tacrolimus in patients undergoing hepatic transplantation. Nonlinear blood binding is a major source of interpatient variation in the disposition of tacrolimus.

Administration, Oral↗
PubMed1988

Effect of cicloprolol in intraocular pressure in healthy volunteers.

Two oral doses of cicloprolol (50 mg and 100 mg), a beta 1-adrenoceptor partial agonist, were administered to nine healthy volunteers in a double-blind placebo-controlled study. Intraocular pressure (IOP) and exercise heart rate were reduced while the resting heart rate and blood pressure remained unchanged. The responses to the two different doses of cicloprolol were similar.

Adolescent↗
PubMed1985

Effect of a hydantoin prostaglandin analogue, BW245C, during oral dosing in man.

Following an open pilot study, the effects of repeated oral doses of BW245C, a hydantoin prostaglandin analogue, were studied in man. Six healthy volunteers received 150 micrograms BW245C or placebo 6-hourly for 5 days according to a double blind randomised balanced design with 7 days interval between treatments. Measurements of headache, facial flushing, heart rate, blood pressure, systolic time intervals, ECG, platelet aggregation responses to ADP and of subjective effects were made before and 1 and 3 h after the first dose of BW245C/placebo on days 1, 3 and 5 of dosing. BW245C produced significantly (p less than 0.05) higher headache scores than placebo on days 3 and 5; facial flushing, nasal stuffiness and abdominal discomfort were more frequent on BW245C than placebo. Heart rate, derived from the ECG, was significantly (p less than 0.05) higher and pre-ejection period significantly (p less than 0.05) shorter on BW245C at 1 h after dosing on each day. Left ventricular ejection time index, QS2 index, PR interval, QRS duration and T wave height were unchanged. Heart rate, counted at the radial pulse, and systolic and diastolic blood pressure, all measured lying and standing, were similar for BW245C and placebo. Platelet aggregation responses were not significantly different between the two treatments. The results indicate that repeated oral doses of BW245C, sufficient to cause moderately uncomfortable subjective effects, do not inhibit platelet aggregation.

Adenosine Diphosphate↗
PubMed1985

Stimulation of dopamine receptors (type 2) lowers human intraocular pressure.

The interaction between bromocriptine and metoclopramide on intraocular pressure (IOP), pupil diameter, and other parameters were studied in healthy volunteers. Pupil diameter was not affected by both treatments and only bromocriptine lowered IOP. Prior treatment with metoclopramide blocked the IOP-lowering effect of bromocriptine. It is concluded that bromocriptine lowers IOP by stimulation of dopamine-2 receptors.

Bromocriptine↗
PubMed1984

A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man.

The effects of 9 beta-methyl carbacyclin, a chemically stable analogue of epoprostenol (prostacyclin, PGI2) were studied, in comparison with epoprostenol, both in vitro and in vivo in man. In vitro 9 beta-methyl carbacyclin and epoprostenol inhibited platelet aggregation induced by ADP, collagen, the endoperoxide analogue U46619 and arachidonic acid. The potency of 9 beta-methyl carbacyclin relative to epoprostenol was comparable in ADP and collagen-aggregated platelet rich plasma (PRP), 9 beta-methyl carbacyclin being 0.01 times as active as epoprostenol. The anti-aggregatory potencies of the two compounds were comparable in PRP and whole blood. The phosphodiesterase inhibitor isobutyl methyl xanthine enhanced the anti-aggregatory activity of both compounds in vitro. 9 beta-methyl carbacyclin and epoprostenol elevated platelet cyclic AMP, 9 beta-methyl carbacyclin being 0.04 times as active as epoprostenol. In a placebo controlled trial both drugs produces significant headache and facial flushing when compared with placebo. Nasal stuffiness, abdominal discomfort and nausea were reported on all three treatments. Both drugs caused significant and comparable increase in heart rate and decrease in pre-ejection (PEP) and PEP/left ventricular ejection time (LVET) ratio compared with placebo. Systolic and diastolic blood pressure, LVET and QS2 index were unchanged. Platelet aggregation responses to ADP were significantly inhibited by all three doses of both drugs compared with placebo. Bleeding time was significantly longer during epoprostenol infusion than either placebo or 9 beta-methyl carbacyclin infusion. Neither drug had significant effect, compared with placebo, on kaolin activated clotting time in PPP, PRP or in PRP in the presence of heparin, prothrombin time, partial thromboplastin time, thrombin clotting time, fibrinogen, fibrinogen degradation products or euglobulin clot lysis time. The pharmacodynamic effects and duration of action of 9 beta-methyl carbacyclin and of epoprostenol are similar; 9 beta-methyl carbacyclin is approximately 100 times less potent than epoprostenol in man.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Bromocriptine lowers intraocular pressure without affecting blood pressure.

Oral bromocriptine (1.25 mg) was given to 8 healthy volunteers in a double-blind placebo controlled cross-over study. 3 and 4 h after taking the tablet there was a significant reduction in intraocular pressure but no change in pupil diameter. There were no changes in heart rate, blood pressure, and systolic time intervals in 6 other healthy volunteers within 3 h of being given 1.25 mg bromocriptine. These results suggest that dopamine receptors may be involved in the control of intraocular pressure.

Blood Pressure↗
PubMed1983

Local and systemic effects of pindolol eye drops.

Local (reduction of intraocular pressure) and systemic (inhibition of exercise-induced tachycardia) effects of 1% and 0.25% pindolol eye drops have been studied in a balanced cross-over double-blind trial in 12 healthy volunteers. Both concentrations produced a comparable reduction in intraocular pressure while the inhibition of exercise tachycardia was significantly less with the lower concentration.

Adult↗