Lipophilicity, interaction with P-gp, and CNS penetration of clinically used ARBs (active metabolite/parent compound, where applicable)
Note that lipophilicity has been reported in a range of different formats; the table uses that which was reported by the cited investigators.
| Measured logP (Octanol:Neutral pH Buffer) | Calculated logP (ALOGPS)a | P-gp Substrate | CNS Penetrationb | |
|---|---|---|---|---|
| Azilsartan/azilsartan medoxomil | −0.29c, pH 7 (azilsartan) | 4.54d | Noc,e (both) | Minimal |
| Candesartan/candesartan cilexetil | −0.96f, −1.7o, pH 7.4 (candesartan) | 4.02 (candesartan) | Yesg | Poorly |
| Eprosartan | 3.57 | ? | ||
| Irbesartan | 1.48f, 1.0o, pH 7.4 | 4.51 | ? | Weakly |
| EXP3174/losartan | 1.19h, 0.08o, pH 7.4 (losartan), −1.22h, −2.45f, −1.6o, pH 7.4 (EXP3174) | 4.50 | Yesi, losartan; Noi, EXP3174 | Poorly |
| Olmesartan/olmesartan medoxomil | −1.2j pH 7.0 (olmesartan) | 2.98 | Nok, olmesartan; Yesk, olmesartan, medoxomil | Poorly |
| Telmisartan | 3.2f, pH 7.4; 2.41l, pH 7.4 | 6.66 | Yesm, telmisartan, acylglucuronide | |
| Valsartan | −0.95f, pH 7.4 | 3.68 | Yesn |
↵a Drug Bank Open Data Drug and Drug Target Database, http://www.drugbank.ca/drugs/DB00966, calculated logP using the ALOGPS algorithm.
↵b Qualitative description taken from regulatory information as summarized in Section VI.B; of note, in some cases published studies have claimed otherwise as discussed in detail in Section III.C; although regulatory information for eprosartan, telmisartan, and valsartan does not mention CNS penetration, published studies indicate penetration with supratherapeutic eprosartan doses and in the majority of telmisartan studies.
↵c Azilsartan label, Japanese regulatory agency-approved prescribing information.
↵d Calculated using ALOGPS algorithm from azilsartan structure.
↵e EMA assessment document EMEA/H/C/002293.
↵f Wienen et al., 2000.
↵g Zhou et al., 2009.
↵h Ribadeneira et al., 1996.
↵i Soldner et al., 2000.
↵j Nakagomi-Hagihara et al., 2006.
↵k Yamada et al., 2007.
↵l Yazdanian et al., 1998.
↵m Ishiguro et al., 2008.
↵n Challa et al., 2013.
↵o Morsing et al., 1999.