Effect of zobo drink (Hibiscus sabdariffa water extract) on the pharmacokinetics of acetaminophen in human volunteers.

Acetaminophen, a common antipyretic-analgesic OTC drug is often administered orally anytime of the day with water or beverages irrespective of possible interactions. Zobo drink, is a sweetened water extract of the dried calyx of Hibiscus Sabdariffa. This work is designed to investigate the effect of zobo drink on an oral dose of acetaminophen. Six healthy male volunteers, ages 28.50 +/- 1.76 years, weighing 62.67 +/- 1.67kg participated in the study. The study was carried out in two phases. In the first phases an oral dose of acetaminophen (1g) was administered to the volunteers and in the second phases, zobo drink was ingested by the volunteers 1.30 h prior the administration of acetaminophen (1g). Acetaminophen concentration in plasma was determined using a validated spectrophotometric method. Pharmacokinetic values obtained were found to be in similar ranges as those previously reported. The absorption parameters t1/2a, Ka, Tmax, Cmax and AUC0-alpha showed no statistically significant changes (p>0.05) after the administration of zobo. There were however statistically significant changes (p<0.05) in Kbeta and t1/2beta of acetaminophen when administered after the zobo drink. This also resulted in 11.69% increase in ClT.

Chronopharmacokinetics of acetaminophen in healthy human volunteers.

Acetaminophen is a common antipyretic-analgesic drug usually administered orally any time of the day. It was however claimed by Belanger et al, (1985) to have a longer elimination half-life (t1/2 beta) in rats when administered by 2100 h, than at 0700 h. This work is designed to investigate this claim in man and to study the circadian changes in acetaminophen pharmacokinetics at three dosing times; 0730 h, 1300 h and 2100 h. Seven healthy male volunteers, age 26.28 +/- 3.01 years, weighing 65.00 +/- 2.2 kg, were administered with 1000 mg oral acetaminophen at the three circadian time after a period of fast of not less than 4 h. The pharmacokinetic values obtained, though varied, are found to be in similar ranges with previously reported values. The absorption parameters ka and mean Tmax were significantly altered with dosing at 0730 h and 2100 h while the mean t1/2 alpha and ka were also significantly changed. There was a significant difference (P < 0.05) between the Tmax values obtained at 2100 h and that of 0730 h, while the 34.9% increase at dosing time 1300 h over 0730 h dosing times is not statistically significant (P > 0.05). Cmax was found to be 22.31 +/- 4.24 mcg/ml for 0730 h dosing time, while a decrease of 9.64 and 11.7% over this value was recorded for dosing time 1300 h and 2100 h respectively. The changes are however not statistically significant (P > 0.05). AUCo-a at 0730 h did not show any significant change when compared with values obtained at 1300 h and 2100 h, but there was a significant difference between the values obtained at 1300 h and 2100 h. Elimination half-life, t1/2 beta was found to be 1.68 +/- 0.67 h at 0730 h. There was an increase of 13.1% and 20.83% over this value at 1300 h and 2100 h. These increases were not statistically significant (p > 0.05). Although there are similar increases in t1/2 beta at the 1300 h and 2100 h dosing time as reported by Belanger et al 1985, the increases were not statistically significant in man.

Pharmacopoeial quality of drugs supplied by Nigerian pharmacies.

BACKGROUND: The quality of medicines available in some less-developed countries is inadequate in terms of content of active ingredient. Reasons for the poor quality of drugs include widespread counterfeiting of medicines in less-developed countries, excessive decomposition of active ingredient as a result of high temperature and humidity, and poor quality assurance during the manufacture of medicinal products. Our aim was to investigate the quality of different drugs obtained from retail pharmacies in two urban areas of Nigeria, and, in instances of poor quality, to ascertain the reason why. METHODS: We randomly collected 581 samples of 27 different drugs from 35 pharmacies in Lagos and Abuja in Nigeria. We analysed the medicines for drug content by validated chromatographic methods, and compared our results with pharmacopoeial requirements. FINDINGS: 279 (48%) samples did not comply with set pharmacopoeial limits, and this proportion was uniform for the various types of drugs tested. Although some preparations contained no active ingredient, most had amounts just outside the pharmacopoeial limits. We identified samples with both too much and too little active drug content. INTERPRETATION: The most probable cause of the poor quality of drugs is absence of adequate quality assurance during manufacture. Substandard drugs sold in the pharmacies of less-developed countries could contribute to global microbial resistance and therapeutic failure of infectious diseases.

Improved RP-HPLC determination of quinine in plasma and whole blood stored on filter paper.

Analysis of quinine in plasma and whole blood samples dried on filter paper is described. Sample preparation involves liquid extraction of plasma and whole blood from the filter paper and subsequent solid-phase extraction using C8 Bond Elut cartridges. A reverse-phase liquid chromatography system with UV detection and fluorescence detection was used. The analytical characteristics of the method are reported, with a quantification limit of 0.1 microg mL(-1) and within an assay coefficient of variation of 5.6-8.4% in plasma and 6.5-12% in whole blood. Representative chromatograms are shown as a function of time for samples from human subjects after ingestion of a single 400-mg dose of quinine sulphate. Quinidine, dihydroquinine and metabolites are well separated from quinine with a resolution of above 1 (Rs>1).

Mefloquine pharmacokinetics in healthy subjects and in peptic ulcer patients after cimetidine administration.

The pharmacokinetics of orally administered mefloquine were determined in six healthy male subjects and in six ulcer patients before and after a 3-day course of cimetidine (400 mg morning and evening). Peak plasma concentrations Cmax and AUC0-infinity were similarly and significantly (P < 0.05) increased after cimetidine pretreatement in both healthy subjects and peptic ulcer patients Cmax was increased by 42.4% and 20.5% while AUC0-infinity was increased by 37.5% in healthy and peptic ulcer subjects respectively. The values of t1/2ab absorption and t1/2 beta elimination, total crearance CLT/F and volume of distribution were altered to varying levels after cimetidine treatment but the changes were not statistically significant in both healthy and peptic ulcer subjects. The established long t1/2 beta and this apparent interaction between mefloquine and cimetidine which resulted in increased mefloquine plasma concentration might be of clinical significant in patients with neurological/psychiatric history.

Effects of cimetidine on the pharmacokinetics of proguanil in healthy subjects and in peptic ulcer patients.

The pharmacokinetics of orally administered proguanil and its metabolites were determined in six healthy volunteers and in six peptic ulcer patients, before and after a 3-day course of cimetidine (400 mg given two times daily for 2 days and 400 mg on the third day 1 h before proguanil). Cimetidine significantly increased Cmax (P < 0.05), AUCo-alpha (P < 0.005) and elimination half-life t 1/2b of proquanil in plasma of healthy subjects. In ulcer patients, cimetidine significantly increased, AUCo-alpha (P < 0.05), elimination half life (P < 0.005) and Cmax. Cimetidine significantly reduced (P < 0.05) Total body clearance in both healthy subjects and in peptic ulcer patients. The Cmax and AUCo-alpha of the active metabolite cycloguanil was significantly decreased (P < 0.05) in both the healthy subjects and in the peptic ulcer patients. The Cmax of the inactive metabolite, 4-CPB was significantly decreased in healthy subjects and AUCo-alpha significantly decreased in peptic ulcer patients.

Effect of temperature on chlorproguanil and proguanil hydrochloride solutions: a chemical stability study.

Chlorproguanil and proguanil hydrochloride solutions in 0.5 M hydrochloric acid, water and 1 M ammonium hydroxide were subjected to different temperatures (22-80 degrees C) for 68 h. The decomposition rate constants for chlorproguanil ranged from 1.60 to 47.6 x 10(3) h-1 in acid, 3.5 to 18 x 10(3) h-1 in water and 3.87 to 32.5 x 10(3) h-1 in base, between 50 degrees C and 80 degrees C. The activation energy Ea was 96.5, 52.12 and 62.1 kJ mol-1 in acid, water and base respectively. The proguanil decomposition rate constant ranged from 1.72 to 18.5 x 10(3) h-1 in acid, 1.58 to 9.67 x 10(3) h-1 in water and 2.34 to 15.77 x 10(3) h-1 in base, between 50 degrees C and 80 degrees C, with Ea values of 54.7, 73.3 and 62.5 kJ mol-1. Three unidentified degradation products were separated in the acid solution for each of the compounds. Chlorproguanil and proguanil are stable (t1/2 values over 30 days and up to 287 days respectively) in acid, water and base at temperatures below 22 degrees C.

Determination of proguanil and metabolites in small sample volumes of whole blood stored on filter paper by high-performance liquid chromatography.

A method is reported for the determination of proguanil and its two metabolites cycloguanil and 4-chlorophenylbiguanide in whole blood and plasma samples obtained by thumbprick and stored dry on filter paper. The sample preparation involves liquid extraction from the filter paper and subsequent solid-phase extraction using C8 Bond-Elut cartridges. Separation and quantification is by a previously reported ion-pairing high-performance liquid chromatographic system with ODS Hypersil as stationary phase and an 50:50 acetonitrile-pH 2 phosphate buffer mobile phase containing 200 mM sodium dodecylsulphate as ion-pairing agent. The analytical characteristics of the method are reported. Representative concentrations are shown as a function of time from a human subject after ingestion of a single 200-mg dose of proguanil hydrochloride. Typical ranges of concentration detected by the proposed method in human subjects were proguanil 12-900 ng/ml, cycloguanil 16-44 ng/ml and 4-chlorophenylbiguanide 1.5-10 ng/ml in whole blood.