Relative bioavailability of chlorothiazide from mucoadhesive compacts in pigs.
The relative bioavailability of chlorothiazide from mucoadhesive polymeric compacts is compared to commercial oral suspension in pigs. A single-dose randomized study was conducted in 12 healthy pigs that are 9-10 weeks old. After overnight fasting, pigs were divided into two groups of six animals. To the first group, a reference product containing 50 mg of chlorothiazide suspension, and in the second group, test product (mucoadhesive compacts) chlorothiazide (50 mg) was administered with 75 mL of water via gastric tubes. Blood samples were collected between 0 to 24 h using catheters inserted into the jugular vein. Plasma was separated by protein precipitation, and chlorothiazide concentrations were determined using a high-performance liquid chromatography method. The mean Tmax and the Cmax of chlorothiazide following the administration of oral suspension and mucoadhesive compacts were 0.58+/-0.20 h and 682.97+/-415.69 ng/mL and 2.17+/-0.98 h and 99.42+/-124.08 ng/mL, respectively. The Kel and T1/2 of chlorothiazide were found to be 1.06+/-0.28 h(-1) and 0.70+/-0.21 h from suspension and 0.95+/-1.11 h(-1) and 2.05+/-1.90 h from the compacts, respectively. The Tmax of mucoadhesive compacts were significantly longer (p<0.05; 2.17 h) than the reference products (0.58 h), whereas the Cmax of compacts were significantly lower (99 ng/mL) than the reference product (683 ng/mL; p<0.05). The area under the curve (AUC) of compacts accounts only 50.15% (404.32+/-449.93 ng h/mL) of the reference product's AUC (806.27+/-395.97 ng h/mL). The relative bioavailability of the compacts was lower than that of the suspension, and this may be due to the narrow window of absorption for chlorothiazide.
Neelam
Karunakar
K
Department of Pharmaceutics & Medicinal Chemistry, T. J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, California 95211, USA.
Mahalingam
Ravichandran
R
Birudaraj
Raj
R
Alfredson
Tom
T
Anne
Pratap
P
Li
Xiaoling
X
Jasti
Bhaskara R
BR
D000818:Animals; D001682:Biological Availability; D002740:Chlorothiazide / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004232:Diuretics / Q000493:pharmacokinetics*; D005260:Female; D008297:Male; D013535:Suspensions; D013552:Swine
D003692:Delayed-Action Preparations; D004232:Diuretics; D013535:Suspensions; D002740:Chlorothiazide