Studies on solubility, bioavailability and hypoglycemic activity of gliclazide p-cyclodextrin complexes

The effect of beta-cyclodextrin ((3-CD) complexation with gliclazide (Gz) on both pharmacokinetic and hypoglycemic parameters of pure drug was evaluated and correlated with its in vitro dissolution. The study involves the preparation of solid inclusion complex of Gz with [3-CD using different techniques. The prepared binary systems showed significant enhancement for in vitro dissolution. The pharmacokinetics of neutralization complex (equivalent to 30 mg of gliclazide) was studied in beagle dogs. Gliclazide plasma levels were measured over a period of 48 h from dosing, using a sensitive HPLC method. Significant changes were observed in the mean values of Gz pharmacokinetic parameters (Cm i K , Tm i K and AUC0.„) between the control and pre-treated groups. The findings of this study suggest that neutralization complex in 1:1 and 1:2 Gz/|3-CD molar ratios was the best in enhancing gliclazide dissolution characteristics and bioavailability. Moreover, the various measures of bioavailability (except AUC) correlated well with both in vitro tests and hypoglycemic activity

Ethnic differences in nifedipine pharmacokinetics and pharmacodynamics: Comparison of middle eastern arabs with other populations

Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P.O.Box 2457, Riyadh 11451. Military Hospital, Riyadh, Kingdom of Saudi Arabia.The pharmacokinetics and pharmacodynamic effects of oral nifedipine were studied in five healthy male Middle Eastern Arab subjects and their results were compared with those reported for other populations. Each subject received a single 2* 10-mg dose under fasting conditions and plasma concentrations were determined by a specific HPLC method. Heart rate and systolic and diastolic blood pressure were also monitored. The elimination half-life, maximum plasma concentration and time to maximum plasma concentration were found to be 3.20±0.21 h, 230.4±36.4 ng/ml and 0.95±0.23 h, respectively. Mean residence time (MRT) and operative clearance (CL/F) were determined to be 3.82±0.67 h and 0.30±0.06 L/h.kg, respectively. Plasma concentrations in Middle Eastern Arab subjects were similar to those reported for South Asians, Japanese and Nigerians, but they were significantly higher than in Caucasians. The AUC and normalized AUC were 2.8 and 3.4 folds greater in Middle Eastern Arab subjects than in Caucasians. The hemodynamic effects of nifedipine were comparable in all ethnic groups studied. In conclusion, Middle Eastern Arab patients should be initiated with a lower dose than would be administered to Caucasians

Population pharmacokinetics of gentamicin in acute lymphoblastic leukemia pediatric patients compared to non-oncology patients

Understanding the pharmacokinetics of gentamicin is essential in special populations, such as pediatric patients with acute lymphoblastic leukemia (ALL), in light of previous studies indicating that ALL patients have a lower volume of distribution than non-ALL patients. Furthermore, validation of such results is needed to ensure their clinical application. Accordingly, this single-center, retrospective, cross-sectional study compares the pharmacokinetic parameters of volume of distribution and clearance (Cl) of gentamicin between ALL and non-ALL patients. Inclusion criteria were pediatric patients aged between 1 and 14 years with or without ALL and receiving intravenous gentamicin for treatment courses > 72 h. Patients’ characteristics, such as age, sex, height, serum albumin, diagnosis, serum creatinine (Scr) concentration, dosing, and pharmacokinetic information, including peak and trough concentrations, were retrieved. The study scrutinized a total of 115 pediatric patients, comprising toddlers (15.7 %), children (76.5 %), and adolescents (7.8 %). All patients received gentamicin every 8 h, with an average dose of 2.50 (0.64) mg/kg. Patients were divided into two groups based on disease state, with 45.2 % (n = 52) in the non-ALL group and 54.8 % (n = 63) in the ALL group. Both groups had similar characteristics in terms of gender, weight, body surface area, and dose. The only significant covariates identified were weight and creatinine clearance (Clcr) for volume of distribution (Vd). A significant difference was found in Scr, Clcr, and blood urea nitrogen (BUN); however, no significant difference between ALL and non-ALL patients emerged in the volume of distribution or Cl. In conclusion, the study findings indicate that dosing requirements were similar between the two groups. Further prospective studies with larger sample sizes are warranted