Sex differences in pharmacokinetics predict adverse drug reactions in women

Table 2 Concordance between sex-biased PKs and VigiBase sex ratios

WHO ATC category	Drug name/PK bias^a	PK measure^b	VB ratio^c	Concordance
Alimentary tract, metabolism	Ondansetron	AUC, C_max	2.14	Concordant
Blood and blood forming organs	Icatibant	AUC, C_max	3.18	Concordant
Cardiovascular system	Metoprolol	AUC, C_max	1.26	Concordant
	Labetalol	C_max, Cl_T	1.50	Concordant
	Nifedipine	Cl_T	1.29	Discordant¹
	Pitavastatin	AUC, C_max	1.12	Discordant²
Systemic hormonal preparations	Methylprednisolone	**AUC, t**_1/2, Cl_T	1.38	Discordant¹
Musculoskeletal	Ibuprofen	*AUC,*C_max, t_1/2, Cl_T	1.46	Discordant¹
Anesthetics, analgesics	Lignocaine	Cl_T	1.64	Condordant
	Propofol	AUC,Cl_T	1.45	Concordant
	Butorphanol	AUC, C_max	3.23	Concordant
	Paracetamol	Cl_T	1.68	Concordant
Anti-epileptics	Ezogabine	AUC, C_max, Cl_T	0.90	Discordant²
Psycholeptics	Clobazam	t_1/2	1.11	Discordant²
	Sertindole	AUC, C_max	1.06	Discordant²
	Thiothixene	Cl_T	1.35	Concordant
	Oxazepam	Cl_T	1.31	Concordant
	Temazepam	t_1/2, Cl_T	1.34	Concordant
	Zopiclone	AUC, C_max	1.55	Concordant
Psychoanaleptics	Memantine	SysExp	1.50	Condordant
	Desipramine	AUC, Cl_T	1.59	Concordant
	Clomipramine	Cl_T	1.57	Concordant
	Paroxetine	Cl_T	2.00	Concordant
	Fluvoxamine	Cl_T	1.73	Concordant
	Mirtazapine	Cl_T	1.53	Concordant
Respiratory	Cetirizine	Cl_T	1.76	Concordant

PK abbreviations: AUC area under the curve, Cmax maximum circulating concentration, Tmax time required to reach Cmax value, t1/2 elimination half-life, ClT clearance time, exposure, or plasma concentration after a fixed time interval, SysExp systemic exposure, DurAbs duration of absorption
^aFont style of drug name indicates direction of PK drug exposure bias: (normal: F > M; bold: M > F)
^bFont style of PK measure indicates direction of greater PK drug exposure: (normal: F > M; bold: M > F; italic: inconsistent)
^cF-to-M reporting ratio of suspected ADRs. Threshold for designation of sex bias = ± 20%
¹False positive
²False negative

ISSN: 2042-6410