Table 5.

Evaluation of possible association between clinical rhabdomyolysis and/or carnitine deficiency and hOCTN2 inhibition. C_max/K_i was computed for compounds in Table 2 and 4.^a Compounds in bold text employ K_i (or IC₅₀) values from literature (i.e. Table 4). Compounds listed in descending order of C_max/K_i value. See Supplemental Table S6 for references 1-65 in this table

Compound name	Ki (μM)	Documented to cause rhabdomyolysis and/or carnitine deficiency in the literature	Cmax (μM) b	Cmax/Ki
Mildronate	26	No	174	6.71
Valproic acid	139	Yes1	159	1.15
Cefazolin	6740	Yes2	1640	0.252
Cefepime	1700	Yes3	378	0.222
Cephaloridine	230	Yes3	41.7	0.181
Cephaloxin	3037	Yes4	74.0	0.135
Gabapentin	1700	No	172	0.101
Ritonavir	7.73	Yes with statin5	0.610	0.079
Omeprazole	14.6	Yes6	0.909	0.0622
Cefoselis	6400	Yes3	174	0.0271
Irinotecan	219	Yes7	5.01	0.0229
Cetirizine	79.8	No	1.73	0.022
Cimetidine	336	No	6.97	0.0208
Vincristine	15.9	Yes8	0.325	0.0204
Cefuroxime	525	Yes9	10.6	0.0201
Grepafloxacin	300	No	5.51	0.0184
Roxithromycin	333	Yes with statin10	6.06	0.0182
Propafenone	74.2	No	0.812	0.0109
Nizatidine	183	No	1.67	0.00911
Vinorelbine	26.8	No	0.133	0.00497
Spironolactone	26	No	0.114	0.00438
Emetine	4.2	Yes11	0.0173	0.00413
Simvastatin	12.4	Yes12	0.0410	0.00331
Cisapride	66.7	Yes13	0.159	0.00239
Metformin	4963	Yes14	10.1	0.00203
Furosemide	1350	No	2.70	0.00200
Ezetimibe	29.3	Yes with statin15	0.0559	0.00191
Ipratropium	30	No	0.139	0.00146
Procainamide	1400	Yes16	1.55	0.00111
Ciclotropium	95	No	0.0206	6.88×10−4
Penfluridol	26.5	No	0.0104	3.93×10−4
Tacrine	500	No	0.134	2.68×10−4
Risperidone	144	Yes with statin17	0.0188	1.31×10−4
Famotidine	1920	Yes18	0.240	1.25×10−4
Daunorubicin	502	No	0.0290	5.78×10−5
Reserpine	32.2	No	0.00181	5.61×10−5
Acebutolol	Not inhibitor	No	2.59	0
Captopril	Not inhibitor	No	3.70	0
Cisplatin	Not inhibitor	Yes19	8.13	0
Digoxin	Not inhibitor	No	0.00282	0
Diphenhydramine	Not inhibitor	No	0.343	0
Lidocaine	Not inhibitor	No	1.21	0
Memantine	Not inhibitor	No	0.26	0
Metoprolol	Not inhibitor	No	0.357	0
Oxaliplatin	Not inhibitor	No	5.91	0
Probenecid	Not inhibitor	No	701	0

^aThe following compounds from Table 2 or 4 are not listed below, since they were previously considered⁹ in evaluating a possible association to hOCTN2 inhibition: zidovudine, lamivudine, ketorolac, levofloxacin, succinylcholine, and procarbazine. Although listed in Table 4, (−)-N-butylscopolamine is not included in Table 5 since its C_max is unknown.

^bValues for C_max in units of μM were computed using compound molecular weight and C_max from the literature. References 20-65 provide literature C_max values for listed compounds in Table 5, respectively. See Supplemental Table S6 for references 1-65 in this table.