PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES OF GLIBENCLAMIDE IN NONINSULIN DEPENDENT DIABETES-MELLITUS

1. The pharmacokinetic and pharmacodynamic properties of oral glibenclamide have been studied in 31 hospitalised in‐patients and 79 ambulant out‐patients with diabetes mellitus. 2. Breakfast was found to have no significant influence on the kinetic behaviour of glibenclamide or on the effect of this drug on blood glucose utilisation. 3. The time course of glibenclamide kinetics after 20 mg dosing was adequately described by a two‐compartment open model, yielding mean half‐lives of 3.3 +/− 1.5 h (t1/2, lambda 1) and 9.7 +/− 1.2 (t1/2, z) for the initial and terminal elimination phases respectively. 4. No significant accumulation or change in kinetic profile occurred in patients who had normal renal and hepatic function, were treated continuously with glibenclamide, and then rechallenged after 8‐12 weeks. 5. Despite inter‐ individual variations in drug absorption, peak plasma concentrations (Cmax) and the area under the plasma concentration‐time curve (AUC(0‐ 24] were dose‐dependent over the dose range 5‐20 mg. No significant dose‐response behaviour was observed in respect of glucose utilisation, suggesting that there is little clinical benefit in using doses of glibenclamide above 5 mg day‐1. 6. Comparison of plasma glibenclamide concentrations at different time‐bands following doses of 5 and 10 mg showed a wider range in ambulant out‐patients than in age‐, sex‐matched in‐patients treated with the same dosages of drug. Mean plasma drug concentrations attained at all time bands up to 8 h after dosing were higher in out‐patients than in in‐patients, suggesting a tendency to ‘over‐compliance’ by patients in anticipation of attendance at clinic. 1990 The British Pharmacological Society