TABLE 7

Impact of cytochrome P450 CYP3A5 genotype on clinical pharmacokinetics

Compound	Estimated CYP3A5 Contribution (In Vitro) %	Clinical Impact of CYP3A5 Reported?	CYP3A5*1 Status^{^a}	N	CL/F	C_max	C_min	References
Compound	Estimated CYP3A5 Contribution (In Vitro) %	Clinical Impact of CYP3A5 Reported?	CYP3A5*1 Status^{^a}	N	% Change Compared with Nonexpressers (CYP3A53/3)			References
Atazanavir	82	Yes	Expresser	15	+39^{^b}	−18	−49^{^b}	Anderson et al., 2009
		Yes	Expresser	12	+42^{^b}			Savic, et al., 2012
Vincristine	75	Yes	Heterozygous	11	+∼100^{^b}^,^{^d}			Egbelakin, et al., 2011
		No	Heterozygous	12	+7			Guilhaumou, et al., 2011
Midazolam	49	No	Heterozygous	22	+12^{^c}			de Jonge et al., 2013
		No	Heterozygous	22	+22	−14		de Jonge et al., 2013
		No	Homozygous	3	+33^{^c}			Goh et al., 2002
		Yes	Heterozygous	13	+27^{^b}^,^{^c}			Goh et al., 2002
		Yes	Expresser	21	+25^{^b}			Elens, et al., 2013
		No	Homozygous	8	−16			Kharasch, et al., 2007
		No	Heterozygous	28	+3			Kharasch, et al., 2007
		No	Homozygous	6	+1			Tomalik-Scharte, et al., 2008
		No	Heterozygous	17	−4			Tomalik-Scharte, et al., 2008
		No	Homozygous	16	−18^{^c}			Floyd, et al., 2003
		No	Heterozygous	23	−13^{^c}			Floyd, et al., 2003
Vardenafil	49	Yes	Homozygous	6	+200^{^b}	−68^{^b}		Shon et al., 2011
		Yes	Heterozygous	7	+89^{^b}	−45^{^b}		Shon et al., 2011
Otenabant	48	Yes	Homozygous	8	+214^{^b}			Goosen et al., 2010
		Yes	Expresser	36	+83^{^b}			Goosen et al., 2010
Verapamil	41	Yes	Expresser	13	+90^{^b}^,^{^e}	−86^{^b}^,^{^e}		Jin, et al., 2007
Tacrolimus	41	Yes	Heterozygous	10	+76^{^b}	−38^{^b}	−58^{^b}	de Jonge et al., 2012
		Yes	Expresser	12	+55^{^b}	−²⁵^{^b}	−50^{^b}	Zheng et al., 2012
		Yes	Homozygous	8	—		−70^{^b}	Kim et al., 2012
		Yes	Heterozygous	44	—		−⁵⁴^{^b}	Kim et al., 2012
		Yes	Heterozygous	53	—		−52^{^b}	Santoro et al., 2013
Rimonabant	36	Yes	Ethnicity Study		+75^{^b}			EMEA, 2009
Indinavir	35	Yes	Expresser	11	+44^{^b}			Anderson et al., 2006
		No	Heterozygous	6	+45			Solas et al., 2007
Cilostazol	24	Yes	Homozygous	4	+49^{^b}			Yoo et al., 2009
		Yes	Heterozygous	20	+34^{^b}			Yoo et al., 2009
Simvastatin	17	No	Expresser	10	−12	+22		Zhou et al., 2013
		Yes	Homozygous	4	+256^{^b}	−44		Kim et al., 2007
		No	Heterozygous	8	+58	−21		Kim et al., 2007
Diltiazem	14	No	Expresser	19	−28	+31		Zheng et al., 2013
		No	Homozygous	3	−38	+51		Yamamoto et al., 2005
		No	Heterozygous	6	−33	+51		Yamamoto et al., 2005
Nifedipine	14	Yes	Heterozygous	3	+171^{^b}	−46		Haas et al., 2013
		Yes	Expresser	5	−50^{^b}			Haas et al., 2013
		No	Heterozygous	8	−30	+4.5		Fukuda et al., 2004
Saquinavir	11	No	Homozygous	16	+52	−29		Josephson et al., 2007
		Yes	Expresser	6	+90^{^b}	−68^{^b}		Mouly et al., 2005
Alprazolam	<10	Nes	Homozygous	5	+40^{^b}	−31^{^b}		Park et al., 2006
		Nes	Heterozygous	7	+16	−²⁸^{^b}		Park et al., 2006
Quetiapine	<10	No	Heterozygous	4	—	+10^{^f}		Nikisch et al., 2011
Oxycodone	<10	No	Expresser	25	—		−6.6	Naito et al., 2011
Erythromycin	<10	No	Expresser	5	+6.3^{^c}			Elens et al., 2013
Everolimus	<10	No	Heterozygous	7	+12	−15	−11	Picard et al., 2011

↵^a Homozygous = *1/*1; Heterozygous = one *1 allele and one other allele (i.e., *3, *6, or *7; Expresser = mixed genotype wherein each subject had at least one *1 allele.
↵^b Denotes clinical findings that were claimed to be statistically significant.
↵^c Denotes clearance determined from an intravenous dose. All other clearance values are CL/F.
↵^d Vincristine demonstrated a two fold increase in metabolite/parent ratio in *1 carriers.
↵^e CL/F and C_max differences were averaged for individual values reported for R- and S-verapamil.
↵^f Value reported is steady-state plasma concentration.