Basic PharmacokineticsREV. 98.10.22
Copyright © 1996 Michael C. Makoid All Rights Reservedhttp://kiwi.creighton.edu/pkinbook/
Miners J, Foenander T, Wanwimolruk S, Gallus A, Birkett D. (European Journal of Clinical Pharmacology) The effect of sulphin- pyrazone on oxidative drug metabolism in man: inhibition of tolbutamide elimination (1982) 22: 321-326.
About the drug:
Tolbutamide is a sulfonylurea which has been used as an oral hypoglycemic agent in non-insulin-dependent Diabetes Miletus with adult onset. In a study using normal, healthy, 70 kg volunteers thefollowing pharmacokinetic data was obtained. Tolbutamide is well absorbed. It is highly protein bound(96%). The volume of distribution is 0.143 L/kg with a half-life of 6.93 hours in normal adults. Tolbutamideis cleared entirely by hepatic function. Dosing: Tolbutamide (Orinase-brand name) is manufactured byUpjohn. Both 250 and 500 mg tablets are manufactured. Both tablet sizes are available for prescription use.The normal daily dose should not exceed 3 grams.
Your consult should contain both an aggressive andconservative dosage regimen recommendations when appropriate as well as calculations where appro-priate.
Extraction ratios are calculated for normal individuals and are considered to be constant.Qr = 0.0191 L/min/kg, Qh = 0.0238 L/min/kg.
In a study presented to you (Int J Clin Pharmacol Ther 1997 Jan; 35(1):43-6) A 500 mgbrand name tablet yielded an AUC of 499 mg/L *hr while a 500 mg generic tablet yielded an AUC of 498mg/L *hr . The Cp
s were 55.1 vs 58.8 mic/mL and the T
s were 4.55 vs 3.82 hr respectively. Thegeneric comes in 250 and 500 mg scored tablets and cost approximately 1/3 of the brand name. You havebeen asked to prepare a recommendation for the P & T Committee for inclusion into the formulary for theHMO. Please give your recommendation and support it with appropriate documentation.(Short paragraph)(Important variables and constants)(Use other side for supportive documentation - appropriate calculations)