A clinical pharmacokinetic microdosing study of docetaxel with Japanese patients with cancer

Abstract

Docetaxel clearance showed marginal nonlinearity between microdose and therapeutic dose, presumably because of saturation of plasma protein binding; however, the magnitude was within twofold, allowing practically acceptable extrapolation.

Clinical pharmacokinetics and drug exposure-toxicity correlation study of docetaxel based chemotherapy in Chinese head and neck cancer patients

“…Relevant publications reporting docetaxel PKs and toxicity or efficacy were retrieved. Twenty-two studies were included, 7 were excluded for lacking of AUC data (26-32), 3 were excluded for the lack of toxicity data (neutropenia) (33)(34)(35), 2 were excluded for liver disfunction enrollment (36,37), and 2 were excluded for the lack of correlation analysis (38,39). Totally, 8 studies were enrolled into this pooled analysis (5,(15)(16)(17)(18)(19)(20)(21).…”

Microdosing drugs: a versatile technique to detect and assess drug–drug interactions

“…First trials that used microdoses in patients (e.g. with cancer) have already been published [8]. Others investigated whether microdosing can be used to evaluate the effect of polymorphisms in SLCO1B1 (gene encoding for OATP1B1) and ABCG2 (gene encoding for BCRP) on OATP1B1 or BCRP substrate disposition [9].…”

Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development

“…However, quantitative prediction of human PK can still be challenging, and phase 0/microdose studies can serve as a powerful complementary tool to existing approaches. Safely obtaining PK data is particularly valuable where a drug has a narrow therapeutic index (NTI), as is often the case with anticancer agents . The pivotal microdosing validation studies in the PK/bioavailability domain have been the CREAM (Consortium for Resourcing and Evaluating AMS Microdosing) and EUMAPP (European Microdosing accelerator mass spectrometry [AMS] Partnership Programme) trials in Europe, and the NEDO (New Energy and Industrial Technology Development Organization) trials in Japan .…”

“…Safely obtaining PK data is particularly valuable where a drug has a narrow therapeutic index (NTI), as is often the case with anticancer agents. 37,42,43 The pivotal microdosing validation studies in the PK/bioavailability domain have been the CREAM (Consortium for Resourcing and Evaluating AMS Microdosing) and EUMAPP (European Microdosing accelerator mass spectrometry [AMS] Partnership Programme) trials in Europe, and the NEDO (New Energy and Industrial Technology Development Organization) trials in Japan. 19,44,45 By now the results of more than 35 studies in both animals and humans have been reported comparing microdose vs. full dose.…”