EFFECT OF IPSAPIRONE ON PLASMA-GLUCOSE AND PHARMACOKINETICS OF IPSAPIRONE IN TYPE-I DIABETICS

Fifteen patients with insulin-dependent diabetes mellitus who were sta bilised on insulin, participated in an open study to assess the short- and long-term effects of ipsapirone on plasma glucose profiles, and t o collect pharmacokinetic data on ipsapirone in this patient populatio n. Plasma glucose concentrations were determined on day 1 (baseline), day 2 (after a single dose of ipsapirone HCl 5mg) and day 7 (after mul tiple doses of ipsapirone HCl 5mg three times daily) of the study. Pla sma ipsapirone concentrations were determined on days 2 and 7. For eth ical reasons, a crossover design could not be used, and the treatment order was the same for all the patients. Consequently, the effect of t reatment (ipsapirone) on plasma glucose concentrations and possible pe riod effects were confounded. Analysis of covariance and correlation a nalysis were used to assess the effect of ipsapirone on plasma glucose concentrations. The geometric means (SD) of the plasma glucose AUC(0- 5h) on days 1, 2 and 7 were 56.9 (1.44), 48.1 (1.60) and 44.7 (1.48) m mol/L . h, respectively. The corresponding geometric mean (SD) trough (Oh) plasma glucose concentrations were 10.0 (1.58), 7.21 (1.96) and 6 .69 (1.79) mmol/L. Correction for differences in trough glucose concen trations by an analysis of covariance indicated that a single dose of ipsapirone HCl does not influence plasma glucose concentrations. Lack of correlation between the individual ipsapirone AUC(0-8h)(ss) on day 7, and the difference between days I and 7 in glucose AUC(0-5h), indic ated that this also applies to multiple doses of ipsapirone. These res ults suggest that the addition of ipsapirone to insulin regimens does not affect plasma glucose levels to such an extent that an adjustment of insulin dosage is required. Plasma ipsapirone concentrations declin e biphasically, with median half-lives of 0.24 hours and 1.71 hours af ter a single dose, and median half-lives of 0.25 hours and 2.03 hours after multiple doses. The maximum concentrations after a single dose a re similar to those after multiple doses, but the AUC(0-8h)(ss) is som ewhat higher than the AUC(0-infinity) (after a single dose), indicatin g slight accumulation of the drug.