Bioavailability of quinidine in congestive heart failure.

Abstract

1 The oral bioavailability of quinidine was evaluated in eight patients with moderate to severe congestive heart failure. Each patient was given a 400 mg dose of quinidine gluconate by intravenous infusion and orally in solution. Serial plasma samples and total urine for drug analysis were collected for 24 and 48 h after drug administration, respectively. 2 When compared to control cardiac patients, the rate of quinidine absorption was slower in the heart failure patients. The mean value for the apparent absorption half-life and time to achieve peak plasma quinidine concentration was 38 + 18 min and 2.4 + 1.5 h, respectively. The corresponding values observed in the control subjects were 18 + 6 min and 1.0 + 0.6 h. 3 The extent of quinidine absorption when evaluated by the AUC and urinary excretion methods was about 72% of the administered dose in the congestive heart failure patients. This value was similar to the extent of quinidine absorption (approximately 73%) observed in the control subjects. 4 A reduction in the plasma clearance rate and apparent volume of distribution for quinidine was observed in the congestive heart failure patients. 5 When compared with non-heart failure cardiac patients, the results of this study suggest that patients with congestive heart failure may require smaller oral quinidine dosages to achieve therapeutic drug concentrations in the plasma or serum.

The pharmacokinetics of enalapril in hospitalized patients with congestive heart failure.

“…If, as found for quinidine (Ueda et al, 1981), a reduction in volume of distribution and clearance is not accompanied by an increase in half-life (effective half-life for accumulation), steady-state concentrations of enalaprilat would be expected to be higher in CHF following multiple dosing of a given dose of enalapril maleate or enalaprilat, but the accumulation ratio would be the same in CHF as found in normals (approximately 1.3) (Till etal., 1984). That is, the concentration of enalaprilat in the body at steady state would be predicted to be approximately 1.3 times that for the first dose of enalapril maleate or enalaprilat.…”

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.…”

“…8) In addition, CL values of midazolam and quinidine (CYP3A4 substrates) after intravenous administration were decreased by 32% and 33% in HF patients, respectively. 9,10) The CL value of theophylline (CYP1A2 substrate) after intravenous administration was markedly decreased in HF patients. 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.…”

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

“…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 .…”