A new similarity method for assessment of pharmacokinetic interaction between flucloxacillin and midazolam

The purpose of this study was to develop a new similarity method to assess the drug-drug interaction between midazolam and flucloxacillin. Total quantum statistical moment (TQSM) of pharmacokinetic profiles were expressed by parameters AUC, MRT, VRT et al. Statistical moment similarity (SMS) expressions were deduced to evaluate the similarity of the converted pharmacokinetic profiles. A trial of the pharmacokinetic interaction between midazolam and flucloxacillin by the SMS method was conducted. For midazolam, total quantum SMS (SMS) was 0.9582; total deviation was 0.0525; total variable probability was 4.18 %; total confidence of probability β was 97.17 % under significance level 0.05; AUC were 334.3±334.1 ng•h•mL^-1 (after administration of midazolam alone) and 206.9±172.2 ng•h•mL^-1 (after co-administration of midazolam and flucloxacillin), respectively. While, for 1'-hydroxy midazolam, SMS was 0.6920; total deviation was 0.3960; total variable probability was 30.80 %; total confidence of probability β was 94.10 % under significance level 0.05; AUC were 1364±810.7 ng•h•mL^-1 (after administration of midazolam alone) and 1637±632.6 ng•h•mL^-1 (after co-administration of midazolam and flucloxacillin), respectively. These results revealed that flucloxacillin might have weak pharmacokinetic interactions on midazolam metabolized into 1'-hydroxy midazolam, indicating that there was weak induction to CYP3A by flucloxacillin and that there was at least 30.80 % of metabolic behaviour in change with bioavailability decreased by 38.11 % that took effect to flucloxacillin metabolism for liver injury in CPY3A4 poor metabolic polymorphisms. SMS can be an optional method applied to characterize and analyze pharmacokinetic profiles.