Table I.

Covariate Effects of Most Common Individual Characteristics on the Pharmacokinetics of Major Anticancer Drugs

Drug	Major covariates	Mathematical association	Recommended dosing	Clinical relevance	Reference
Busulfana	WT	CL = 4.04 L/h/20 kg·(WT/20) 0.74	1.1 mg/kg for children ≤12 kg	Improve target AUCbusulfan	(56)
			0.8 mg/kg for children >12 kg	(900–1,350μmol h/L)
Docetaxelb	HEPc	CL = BSA(36.8–4.6·AAG-0.14·AGE)·(0.58·HEP)	~60% dose in pts with elevated	Avoid (febrile) neutropenia	(39)
			Liver enzymesc
Melphalana	WT, GFR	D(mg) = 9·(0.34·WT + 0.038·GFR)	Proposed nomogram	Improve target AUCmelphalan (9μg h/mL)	(62)
Methotrexate	COM, GFR	CL = 8.8 + 0.04·(87 − GFR) − (2.45·PPI) − (1.46·NSAR)	Avoid NSAR	Avoid nephrotoxicity, mucositis and myelosuppression	(75)
			Potentially avoid PPI
Paclitaxelb	SEX	VMEL = 37.4·1.2Sex·(BSA/1.8)0.84·(Age/56)0.35	200 mg/m2 in male patients	Avoid severe neutropenia	(73)
			175 mg/m2 in female patients
Pemetrexed	GFR	CL = 43 + 47.2·(GFR/92.6)	Avoid when GFR <45 ml/min	Avoid severe neutropenia	(76)
Temozolomide	BSA	ln(CL) = ln(4.87) + 1.14·ln(BSA)d	150 mg/m2 for 5/28 days	Avoid severe neutropenia	(65)
Topotecan	GFR, WT	CL = (5.7 + 12.8·GFR/70)·(WT/70)0.75	0.75 mg/m2 for 5/28 days	Avoid severe neutropenia	(80)
			if GFR 20–40 ml/min

Ref reference, WT weight, HEP hepatic enzymes, AUC area under-the concentration–time curve, SEX patient gender, BSA body surface area, PPI proton pump inhibitors, NSAR nonsteroidal antirheumatic drugs, CL drug clearance (liters per hour), D dose, GFR glomerular filtration rate (ml/min/1.73 m²), VM _EL maximum elimination capacity (micromoles per hour), COM comedication

^aIn children

^bAnalysis performed in patients receiving 3-weekly docetaxel/paclitaxel

^cEither GGT, alkaline phosphatase, ALT, AST

^dFor male patients