Effect of Congestive Heart Failure on Mexiletine Pharmacokinetics in a Japanese Population

Abstract

082 l/h/kg, mean؎S.D., pϽ0.05). Further, the CL/F ratio was 50% lower in group NYHA III-IV when compared with the Non-CHF group, and the CL/F ratio tended to change in inverse proportion to NYHA class. Conclusion: CHF status significantly affects mexiletine clearance. Therefore, dose adjustments and careful monitoring are likely required in CHF patients receiving mexiletine.

Pharmacokinetics of R- and S-Carvedilol in Routinely Treated Japanese Patients with Heart Failure

“…On the other hand, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP3A5*3, UGT2B7*2, UGT2B7*3, and the C3435T mutation of MDR1 did not affect the pharmacokinetics of R-and S-carvedilol in healthy Japanese. 2,6) Several pharmacokinetic studies have suggested that hepatic elimination of certain drugs via oxidative metabolism is impaired in patients with heart failure (HF) [7][8][9][10][11][12][13] ; that is, the CL/F value of prazosin after oral administration in HF patients was 46% of that in healthy subjects. 7) It was also reported that the CL/F value of aminopyrine after oral administration in HF patients in the aminopyrine breath test was 24% of that in control subjects.…”

“…11,12) Recently, population pharmacokinetic analysis has revealed that the CL/F value of mexiletine, which is mainly metabolized by CYP1A2 and CYP2D6, is reduced significantly in HF patients as compared with non-HF patients. 13) However, it is still unclear whether the pharmacokinetics of R-and/or S-carvedilol is altered by HF. In the present study, therefore, we investigated the pharmacokinetics of R-and S-carvedilol in routinely treated Japanese patients with HF.…”

The influence of heart failure on the pharmacokinetics of cardiovascular and non‐cardiovascular drugs: a critical appraisal of the evidence

“…By contrast, other studies did not report any significant differences in volume of distribution and elimination half‐life of lidocaine between HF patients and controls . The clearance of mexiletine was significantly reduced (−33%) in HF patients in one study , but not in another . No significant pharmacokinetic changes in HF patients were observed with procainamide in four studies, barring a significant reduction (between −17% and −49%) in clearance in two studies .…”

“…A total of 59 studies (49 on cardiovascular drugs) investigating 36 drugs (31 cardiovascular) were identified (Tables ). Twelve studies were published in the period 1970–1979 , 20 in the period 1980–1989 , 12 in the period 1990–1999 , 10 in the period 2000–2009 , and five in the period 2010–2018 .…”

“…Theophylline, n/a, i.v. [48] PPK: n = 200, age n/a, 95M/105F HF subgroup: n = 51, NYHA, age and M/F n/a Yes Yes n/a n/a n/a n/a n/a clearance of mexiletine was significantly reduced (À33%) in HF patients in one study [86], but not in another [61]. No significant pharmacokinetic changes in HF patients were observed with procainamide in four studies, barring a significant reduction (between À17% and À49%) in clearance in two studies [62][63][64]75].…”