Effect of selected compounds on SCr, CLcr, and GFR in humans and the correlation with in vitro inhibition of OCT2, MATE1, and MATE2K

InhibitorsDosing RegimenSCr ↑CLcrGFR↓Markers for GFRCmaxfuCmax/IC50aCmax,u/IC50aReferences
Cimetidine400 mg (QDS)13–2620NS51Cr–EDTA,inulin8–120.84.1420.002.143.3116.001.71Dutt et al., 1981; Hilbrands et al., 1991
Pyrimethamine50–100 mg SD18–2625–27NSinulin2.3a0.133.77115.0051.110.4914.956.64Opravil et al., 1993; Kusuhara et al., 2011
Famotidine40 mg QD, 7daysNSNS0.390.80.020.870.060.010.690.05Ishigami et al., 1989
Famotidine200 mg SD; 160 mg q4hSISI1. et al., 2015
Ranitidine300 mg QDNSNS3.720.850.320.450.180.270.390.15Motyl, 2004
Trimethoprim20 mg/kg/day (10 days); 200 mg BID3116NS51Cr–EDTA iothalamate3.4–6.90.560.3513.5349.290.207.5827.60Naderer et al., 1997; Arya et al., 2014
Dronedarone400 mg BID 7days10–1518NSSinistrin, PAH0.300.020.160.650.030.0030.0130.001Tschuppert et al., 2007
DX-619800 mg (QD) (4 days)30–4026NSIohexol20.5–220.29–0.35b23.4026.83220.08.199.3977.0Sarapa et al., 2007
Dolutegravir50 mg (QD or BID, 14 days)9–1710 –14NSIohexol Cystatin C6.7–13.10.0162.383.641.050.620.040.01Koteff et al., 2013
Cobicistat150 mg QD, 7 days, PO10.5, 238–14, 9 – 20NSIohexol1.550.030.041.580.080.0010.050.002Cohen et al., 2011; German et al., 2012; Arya et al., 2014
Ritonavir100 mg QD25NSIohexol2.160.0150.097.710.050.0010.120.001Deray et al., 1998; German et al., 2012; Lepist et al., 2014
Ranolazine1000 mg BID, 5 days, PO1210NSSinistrin6.010.380.130.360. et al., 2014
Rilpivirine25 mg (QD, 96 weeks)10NSCystatin C0.60.0051.582.402. label; Maggi et al., 2014
Amiodarone400 mg QD110.8– et al., 1993
Raltegravir400 mg BIDNSNS3.380.17<0.03<0.03<0.03<0.01<0.01<0.01Drug label; Maggi et al., 2014; Rizk et al., 2014
Telaprevir750 mg q8hSINSCystatin C, L–FABP, NAG5.820.04–0.24b<0.060.09<<0.01Suzuki et al., 2013; Matsui et al., 2015
Vandetanib300 mg QD150.330.10.835.508.250.080.550.83Shen et al., 2013
  • —, data are not reported or available; BID, twice daily; L-FABP, liver-type fatty acid binding protein; NAG, N-acetyl-β-Dglucosaminidase; NS, not significant (either statistically or clinically); PAH, para-amino-hippurate; PO, by mouth; QDS, four times a day; q4h, every 4 hours; q8h, every 8 hours; SD, single dose; SI, significantly increased compared with baseline level.

  • a IC50 values used were generated at Merck & Co. and shown in Table 1, except for DX-619, for which the lowest IC50 value obtained from the literature is used (see Table 1).

  • b Highest fu values are used to estimate Cmax,u/IC50 as the worst-case scenario.