The Effect of Methyldopa on Renal Function in Patients With Renal Insufficiency

Ek, Brodwall; Myhre, E; Stenbaek, O; Hansen, Tonya Moen

doi:10.1111/j.1365-2796.1972.tb00061.x

Journal of Internal Medicine

1972

DOI: 10.1111/j.1365-2796.1972.tb00061.x

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The Effect of Methyldopa on Renal Function in Patients With Renal Insufficiency

Brodwall Ek¹,

E Myhre²,

O Stenbaek³

et al.

Abstract: Renal function studies have been performed before and during treatment with methyldopa in ten patients with different degree of renal functional impairment. Effective renal plasma flow increased during treatment in patients both with slight and advanced renal failure. However, ever, the glomerular filtration rate decreased slightly in several cases despite increased renal plasma flow. The renal hemodynamic effects of methyldopa could not be related to the serum concentrations of unconjugated methyldopa. The pr… Show more

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Cited by 5 publications

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The pharmacokinetics of α-methyldopa in dogs

Kochak

Mason

1985

Journal of Pharmacokinetics and Biopharmaceutics

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alpha-Methyldopa was intraarterially and orally administered to dogs at two dose levels in a randomized complete crossover design. The appearance of secondary peaks in the plasma concentration-time profiles indicated the presence of enterohepatically recycled methyldopa. This was established by the absence of a secondary peak following readministration of a dose after biliary cannulation and the detection of methyldopa in the bile of a cannulated dog. Enterohepatic recirculation was estimated to account for a mean of 16.2% of the area under the plasma concentration-time profile after intraarterial administration. Total systemic clearance, defined as the sum of elimination by all routes from the general circulation of the administered dose, and corrected for enterohepatic recirculation, averaged (+/- SD) 99.4 +/- 24.6 ml/min in the dog. An extended average apparent terminal half-life of 6.0 +/- 5.2 hr was exhibited after oral administration compared to an average half-life of 3.1 +/- 1.8 hr following intraarterial administration. Elimination kinetics were linear in the dose range studied. Oral plasma concentration data suggest that the apparent bioavailable fraction may be dose dependent.

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The pharmacokinetics of α-methyldopa in dogs

Kochak

Mason

1985

Journal of Pharmacokinetics and Biopharmaceutics

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The Adrenergic Inhibitors

Weber¹,

Graettinger²,

Drayer³

1987

Medical Clinics of North America

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Clinical Pharmacokinetics of Methyldopa

Myhre

Rugstad

Hansen

1982

Clinical Pharmacokinetics

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Absorption of methyldopa from the gastrointestinal tract is incomplete and variable; bioavailability after oral administration is about 25% (range 8 to 62%). The average time to reach maximum plasma concentration (tmax) [chemically determined] is 2 hours, when the maximum plasma concentration of active drug accounts for 50% of the radioactivity, the remainder representing various metabolites. Physicochemical determination of methyldopa shows that bi-phasic elimination occurs after both intravenous and oral administration, the half-life of the alpha-phase being 0.21 hours (range 0.16 to 0.26 hours) and of the beta-phase 1.28 hours (range 1.02 to 1.69 hours) in normal subjects. Methyldopa is less than 15% protein bound, whereas the primary metabolite, which most probably is the O-sulphate, is about 50% protein bound. The apparent volume of distribution in the central compartment is about 0.23L/kg (range 0.19 to 0.32L/kg), and the total volume of distribution (calculated as Vdarea) is about 0.60L/kg (range 0.41 to 0.72L/kg) in healthy volunteers. Acid-labile conjugates are formed after oral administration. These acid-labile conjugates, in particular the O-sulphate, are probably formed in the intestinal cells, since they are detected in very small amounts after intravenous administration. Additionally, there is a rapid formation of partly unidentified metabolites after both intravenous and oral administration. After intravenous administration the quantitatively most prominent metabolites are methyldopamine and the glucuronide of dihydroxyphenylacetone, but traces of 5 or 6 other metabolites have also been found and identified. These metabolites are probably formed in the liver, but the complete metabolic pattern is still unknown. The renal clearance of methyldopa (95 ml/min/m2) is more than 50% higher than the endogenous creatinine clearance. Renal excretion of some metabolites is slower. Extrarenal elimination accounts for about 50% of the total body clearance of the drug. Renal excretion is very low in patients with renal failure, resulting in accumulation of both active drug and, in particular, its metabolites. There is a marked accumulation of unidentified metabolites in renal failure patients, which possibly explains the strong and prolonged hypotensive action of methyldopa in these patients.

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The Effect of Methyldopa on Renal Function in Patients With Renal Insufficiency

Cited by 5 publications

References 7 publications

The pharmacokinetics of α-methyldopa in dogs

The pharmacokinetics of α-methyldopa in dogs

The Adrenergic Inhibitors

Clinical Pharmacokinetics of Methyldopa

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