The influence of malnutrition on the oral pharmacokinetics of nimesulide in rats.

Malnutrition is a health problem in Mexico. It has been established that malnutrition may produce important changes in the pharmacological response to drugs, since changes in the pharmacodynamics and pharmacokinetics may occur. It has been described that a reduction of plasma proteins and in hepatic enzymes may occur. Due to these changes, absorption, distribution and elimination of drugs can be modified. Nimesulide is a non-steroidal anti-inflammatory agent that is widely used. This drug is importantly bound to plasma proteins and is metabolized through cytochrome P-450, two systems that are altered in malnutrition. In order to establish if malnutrition can modify the pharmacokinetics of nimesulide, a comparison of pharmacokinetic parameters obtained in control and protein-calorie malnourished rats was carried out. Two groups of 7 rats were employed in this study. At 45 days of age, group 1 received a standard balanced diet for 4 weeks, whereas, group 2 received a low protein diet for the same period. Then, rats received an oral dose of 10 mg/kg nimesulide and blood samples were drawn at selected times for 12 hr. Nimesulide whole blood levels were determined by HPLC and the pharmacokinetic parameters; Cmax 1.18 +/- 0.13 and 1.03 +/- 0.10 microg/ml, tmax 5.25 +/- 1.03 and 7.48 +/- 1.09 h and AUC12h 8.64 +/- 1.19 and 8.27 +/- 0.85 microg x h/ml were obtained. We conclude that malnutrition does not modify the oral pharmacokinetics of nimesulide.

Effect of age on the pharmacokinetics of ranitidine in healthy Mexican volunteers.

UNLABELLED: Numerous reports in the literature have demonstrated changes in drug pharmacokinetics that result with age. Ranitidine is a drug commonly used in Mexico. However no reports on the pharmacokinetics of ranitidine in the Mexican population are available in the literature. The objective of this clinical trial was to evaluate the effect of age on the pharmacokinetics of ranitidine in healthy Mexican volunteers. METHODS: Twenty-one healthy Mexican volunteers were included, who were divided into three groups G1 (18-30 y), G2 (31-50 y) and G3 (51-60 y). The volunteers were given a single oral dose of 300 mg of ranitidine and blood samples were obtained, and some pharmacokinetic parameters were correlated with age. RESULTS: Statistically significant differences were noted in the distribution volume (4.00 +/- 1.11 L/kg in G1, vs 2.15 +/- 1.12 L/kg in G3) of the drug. Clearance was faster among the G1 (1.11 +/- 0.12 mL/hr) group compared to the G3 group (0.58 +/- 0.19 mL/hr). Differences for AUC, t1/2 and Cmax are more evident between G1 and G3. DISCUSSION: The results of our study indicated that in patients over 50 years of age who are treated with ranitidine, the dosage of this agent should be appropriately adjusted in order to avoid adverse effects that may develop with prolonged use of the drug. However it is very important to consider that our result only reflect observations made from a single dose study, thus it is necessary to carry out study under chronic dosage treatment.

Effects of gender and phase of the menstrual cycle on the kinetics of ranitidine in healthy volunteers.

The present study was undertaken to determine if differences exist in the pharmacokinetic parameters of oral ranitidine caused by gender and stage of the menstrual cycle. The study was performed in two steps, in the first a pharmacokinetic study was performed on 10 men (average age 35.5 yrs) and 10 women (average age 34.7 yrs) during the follicular phase, and in the second the pharmacokinetic study was performed only on the same women in their luteal phase. Subjects received a tablet dose of 300 mg ranitidine, and blood samples were drawn at several times after its ingestion. Plasma ranitidine concentration was determined by high performance liquid chromatography. Comparison of the pharmacokinetic parameters of women and men revealed statistically significant differences both in distribution volume (Vd) with values of 2.0 and 6.3 l/kg, Area Under Curve (AUC) with values of 7312.15 and 11471.94 ng/ml/h, and clearance (CLt) with values of 0.65 and 0.59 l/kg/h, respectively. Several pharmacokinetic parameters in women were different in the follicular compared to the luteal phase; for example, Vd was 2.0 and 5.6 l/kg, AUC was 7312.15 and 5195.83 ng/ml/h, and CLt was 0.65 and 0.97 l/kg/h, in the respective phases. Moreover, the maximum concentration (Cmax) was 1086 ng/ml in the follicular vs. 864 ng/ml in the luteal phase. The first study detected differences between men and women in several pharmacokinetic parameters, mainly those indicative of drug availability, for example, Vd, AUC, and CLt. Comparison of data obtained in the follicular phase with those obtained in the luteal phase revealed differences in most pharmacokinetic parameters, which is seemingly indicative of the characteristic physiological changes associated with the luteal phase that largely affect the kinetics and availability of drugs such as ranitidine. Although it has been postulated that hormonal fluctuation within the menstrual cycle phase is the primary cause of documented gender differences in the pharmacokinetics and pharmacodynamics of drugs, further study of related factors is required to understand how gender and menstrual cycle rhythms affect the phannacokinetic process in their entirety.