First dose in neonates: pharmacokinetic bridging study from juvenile mice to neonates for drugs metabolized by CYP3A
- Resource Type
- Authors
- Wen-Qi Wang; Bo-Hao Tang; Min Kan; Guo-Xiang Hao; Wei Zhao; Bin Du; Xi-Ting Liu; Yue Zhou; Xin Huang; Pan-Pan Ye; Yi Zheng; Feng Yu; Le-Qun Su
- Source
- Xenobiotica. 50:1275-1284
- Subject
- CYP3A
Midazolam
Health, Toxicology and Mutagenesis
Pharmacology
Toxicology
Models, Biological
030226 pharmacology & pharmacy
Biochemistry
Mice
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Dose prediction
Animals
Cytochrome P-450 CYP3A
Medicine
Juvenile
Computer Simulation
business.industry
Clindamycin
General Medicine
030220 oncology & carcinogenesis
business
medicine.drug
- Language
- ISSN
- 1366-5928
0049-8254
First dose prediction is challenging in neonates. Our objective in this proof-of-concept study was to perform a pharmacokinetic (PK) bridging study from juvenile mice to neonates for drugs metabolized by CYP3A. We selected midazolam and clindamycin as model drugs. We developed juvenile mice population PK models using NONMEM. The PK parameters of these two drugs in juvenile mice were used to bridge PK parameters in neonates using different correction methods. The bridging results were evaluated by the fold-error of 0.5- to 1.5-fold. Simple allometry with and without a correction factor for maximum lifespan potential could be used for a bridging of clearance (CL) and volume of distribution (V