Hassan M. Ali

Pharmacokinetics of praziquantel in healthy volunteers and patients with schistosomiasis.

The pharmacokinetics of a novel praziquantel preparation (Distocide) were investigated in Sudanese patients with hepatosplenic schistosomiasis and in healthy volunteers, and compared with those of Biltricide. The results of the first study indicated greater (P less than 0.05) plasma concentrations of Biltricide at 1.5, 2, 3 and 5 h after administration than with Distocide; plasma elimination half-lives (t 1/2) were not significantly different. In patients with hepatosplenic schistosomiasis, higher plasma levels of Distocide were noted (P less than 0.05 at 8 h) compared to healthy controls; however, due to wide inter-individual variations, there were no significant differences in maximum plasma concentration, time to maximum plasma concentration, area under the plasma concentration curve (AUC), volume of distribution, or clearance; t 1/2 was greater (P less than 0.05) in patients (11.9 +/- 5.4 h) than controls (2.3 +/- 0.4 h). In the presence of food, higher plasma concentrations of Distocide occurred compared to the fasting state; AUCs were greater (P less than 0.01) in both food groups, although the values of t 1/2 were shorter. The lower plasma levels and longer duration of action of Distocide may be advantageous in reducing side effects and prolonging exposure of the schistosomes to the drug.

The effect of sudanese diet on the bioavailability of ampicill1n

Abstract The effect of time of a typical Sudanese diet on the bioavailability of orally administered ampicillin has been examined. Using the urinary excretion method the extent and rate of ampicillin bioavaiiability from commercially available capsules were determined. Different results were obtained, upon changing the time of ampicillin administration with respect to the food intake. Our results indicate that for maximum absorption of ampicillin the capsules should be taken at least two hours before food.

Oltipraz: administration with food increases its anti-schistosomal activity

In a previous study it was demonstrated that the concentration of oltipraz in the plasma of human volunteers was significantly elevated when administered with food. In this study we attempted to determine if this food-induced increase was associated with an increase in the drugs anti-schistosomal activity. The drug was administered with and without food to two groups of patients infected with Schistosoma mansoni. The concentration of oltipraz in the plasma of these patients was measured at varying intervals after dosing. Results indicate that the food-induced increase in the bioavailability of oltipraz in patients with S. mansoni produces a significant increase in the drugs anti-schistosomal activity.

Effect of Cysteine on Oltipraz Blood Levels in Green Monkeys (Cercopithecus aethiops)

Oral coadministration of oltipraz, an antischistosomal compound, with cysteine to green monkeys (Cercopithecus aethiops) led to a marked increase in both the extent and rate of oltipraz bioavailability. The drug blood levels were monitored using a single extraction gas-liquid chromatographic assay. When 6 healthy adult animals were given oltipraz together with cysteine in a crossover study, peak serum concentrations, areas under the curve and absorption rate constants of oltipraz were on average 7 times greater than when the drug was administered alone. Oltipraz peak serum concentrations were reached 1 h earlier as a result of cysteine administration (2 h after dosing). At present, the mechanisms responsible for the effect(s) of cysteine on oltipraz bioavailability have not been identified. The marked increase in oltipraz bioavailability produced by coadministration of cysteine, irrespective of the exact mechanisms involved, may have significant clinical implications with regard to the treatment of schistosomiasis. Our results also indicate that oltipraz blood levels seem to be influenced by some sex-related factors. Male monkeys had higher oltipraz blood levels than females. These sex-induced differences were more evident in oltipraz-cysteine-treated monkeys.

Comparative bioavailability of eight brands of ampicillin

Abstract Using a chemical method of assay, the bioavailability of ampicillin in healthy human volunteers has been examined. The urinary excretion method was used to determine the extent and rate of bioavailability following oral administration of 500 mg capsules produced by 8 different manufacturers. The brand Omnipen was used as the reference product. The results indicate that the different brands are not bioequivalent.

Paracetamol bioavailability from an elixir, a suspension and a new alcohol-free liquid dosage form in humans

Paracetamol (acetaminophen) bioavailability and pharmacokinetics were examined following oral administration of 1.44 g single doses of paracetamol alcohol-free solution A, suspension B and an elixir C to 8 healthy male volunteers. The drug plasma concentrations were measured using an HPLC method. The mean AUC (μg/h/ml), peak plasma concentration (PPC; μg/ml) values (X ± S.E.) obtained following dosing with A (78.11 ± 5.88 μg/h/ml−1 and 23.36 ± 1.71 μg/ml) were significantly higher than those for B (65.12 ± 4.55 μg/h/ml and 17.67 ± 1.97 μg/ml). The (PPC) was reached in a shorter time after dosing with A (52.50 ± 9.4 min) compared to B (86.25 ± 15.5 min) and C (67.5 ± 13.6 rmmin). The rate of paracetamol absorption, Ka (h−1) was highest after dosing with A (3.58 ± 0.52 h−1) followed by C (3.09 ± 0.48 h(su−1) and then B (2.81 ± 0.56 h(SU−1))0.

Correlation between microbiological and chemical assay of ampicillin in bioequivalence studies in man

Abstract Using the urinary excretion method, the bioavailability of ampicillin from two commercially available brands was investigated. The amounts of ampicillin in urine were determined chemically and microbiologically. The results indicate good agreement between the chemical and microbiological assay methods. The chemical assay was recommended as the method of choice for the assay of ampicillin in bioequivalence studies. Using this method the two brands were found not to be bioequivalent.

The effect of sudanese food and chloroquine on the bioavailability of ampicillin from bacampicillin tablets

Abstract The effect of Sudanese food and chloroquine on the bioavailability of ampicillin from bacampicillin was investigated. The bioavailability of ampicillin was determined using the urinary excretion method. The urinary levels of ampicillin were measured chemically. Bacampicillin capsules were administered: (i) under different dietary conditions; and (ii) on an empty stomach together with chloroquine phosphate tablets. Unlike the case of ampicillin capsules, neither food nor chloroquine affected the bioavailability of ampicillin from bacampicillin capsules. The difference between ampicillin and bacampicillin capsules with respect to the effect of food and chloroquine on ampicillin bioavailability is discussed.

Chloroquine and premature evacuation of uterine conceptus in rats

Bilateral spaying on day 18 of pregnancy in rats made the refractory uteri highly reactive to a single injection of chloroquine (25 mg/kg). Complete evaluation of the uterine conceptus resulted by 24-48 hours following chloroquine administration. It was moreover observed that the amount of luteal progesterone which was found to be sufficient to maintain pregnancy until term, failed to reverse the abortifacient efficacy of chloroquine.

Investigations on the influence of liver diseases on ampicillin body levels in man

Ampicillin bioavailability was examined using the urinary excretion method, in healthy subjects and patients with: viral hepatitis, primary hepatocellular carcinoma and hepatosplenic schistosomiasis. A single dose of 500 mg ampicillin was administered intravenously in each case. Viral hepatitis patients gave similar results to healthy subjects. Primary hepatocellular carcinoma and hepatosplenic schistosomiasis patients had reduced drug bioavailability compared to healthy subjects (P less than 0.001).