Pharmacological evaluation of hydroxypropylcellulose-ethylcellulose microcapsules containing piretanide.
Hydroxypropylcellulose (HPC)-ethylcellulose (EC) microcapsules containing piretanide prepared by a solvent evaporation technique, were evaluated on pharmacokinetic, pharmacodynamic and pharmacological parameters in spontaneously hypertensive rats (SHR). HPC-EC10 (5:3) microcapsules showed sustained plasma piretanide levels and almost the same AUC (area under the curve) as compared with piretanide solution. Effect of treatment with the microcapsules (single oral administration per day in doses of 10 and 30 mg/kg) and the solution (double oral administration per day in doses of 5 and 15 mg/kg) was examined for 4 weeks on urine volume and urinary electrolytes excretion and blood pressure. The microcapsules and solution induced dose-dependent diuresis throughout the experimental period and a reduction in blood pressure from 2 weeks of the treatment. HPC-EC10 (5:3) microcapsules containing piretanide were satisfactory as a sustained-release preparation in the light of the anti hypertensive effect even at a half frequency of daily dosing of the solution.
Pharma Research Laboratories, Hoechst Japan Limited, Saitama.
T
T
Tsujiyama
N
N
Suzuki
T
T
Kuriki
M
M
Kawata
S
S
Goto
D000284:Administration, Oral; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002482:Cellulose / Q000031:analogs & derivatives; D004232:Diuretics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004334:Drug Administration Schedule; D004339:Drug Compounding; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
D004232:Diuretics; D013449:Sulfonamides; D000450:Aldosterone; C013517:ethyl cellulose; D002482:Cellulose; C008079:hydroxypropylcellulose; C015451:piretanide; D012083:Renin