Abstract
【Objective】 Clinical pharmacokinetic information on 28 anti-diabetic agents for systemic application released by pharmaceutical companies in Japan was surveyed and analyzed to explore whether the said information is in line with the intended original purpose for facilitating effective, safe pharmacotherapy.
【Method】 Pertinent information was gathered from Drug Interview Forms edited by pharmaceutical companies and from review reports and Common Technical Documents (CTDs) submitted for marketing approval application.
【Results】 F values (bioavailability data) were retrieved for 13 drugs, and the Ae data (urinary excretion rate of unchanged drug) for 7 drugs, Vd (volume of distribution) data for 13 drugs, CLtot (total clearance) data for 12 drugs, and fuP (fraction unbound in plasma) data for 24 drugs. Data on all of the five parameters, namely, F, Ae, Vd, CLtot and fuP, could be collected only for 7 drugs. Nine drugs were noted to have the characteristic of being binding-insensitive (IS; fuP > 0.2), and 15 of having the characteristic of being binding-sensitive (S; fuP < 0.2). For 21 drugs, clinical pharmacokinetic studies were performed, including measurements of the plasma total drug concentration, and measurements in patients with impaired renal function and those with impaired hepatic function. With regard to drugs that have the characteristic of being binding-sensitive, it entails the risk of determining whether it is necessary to adjust the dosage and administration based solely on the percent changes in the plasma total drug concentration, so that information on the percent changes in the fraction of the unbound drug in the plasma in patients with organ dysfunction as opposed to those in normal healthy individuals is essential and vitally important; yet it was in only in those patients with impaired hepatic function receiving ipragliflozin or dapagliflozin that this parameter was measured.
【Conclusion】 The existing status was shown to be inadequate in terms of providing sufficient information for allowing a precise judgment of the dosage and administration according to the patients’conditions.
