European Journal of Clinical Pharmacology

, Volume 8, Issue 6, pp 381–386

Plasma concentration of α-methyldopa and sulphate conjugate after oral administration of methyldopa and intravenous administration of methyldopa and methyldopa hydrochloride ethyl ester

  • J. A. Saavedra
  • J. L. Reid
  • W. Jordan
  • M. D. Rawlins
  • C. T. Dollery
Originals

DOI: 10.1007/BF00562310

Cite this article as:
Saavedra, J.A., Reid, J.L., Jordan, W. et al. Eur J Clin Pharmacol (1975) 8: 381. doi:10.1007/BF00562310

Summary

The plasma concentrations of free α-methyldopa and methyldopa sulphate conjugate were measured in 7 hypertensive patients with normal renal function following α-methyldopa (1 g) orally. Five of these patients subsequently received α-methyldopa ethyl ester (250 mg) (methyldopate) intravenously and two further patients received 250 mg of α-methyldopa intravenously. After oral administration a large amount of total plasma α-methyldopa was present as sulphate conjugate. There were wide interindividual differences in the ratio of free: conjugated α-methyldopa in plasma (ratio at 4 hours ranged from 3.73 – 0.83) suggesting that individual differences in the extent of sulphate conjugation may occur. There was no close correlation between the degree of conjugation and the fall in arterial pressure. At all time intervals examined, plasma concentrations were higher following intravenous α-methyldopa than α-methyldopate. The plasma concentration of α-methyldopa (free and esterified) 60 minutes after i.v. α-methyldopate was 1.7±0.3 µg/ml wile at the same time after the same dose of methyldopa by the same route the mean concentration was 5.9 µg/ml. Although small amounts of sulphate conjugate were detected after i.v. α-methyldopate, insignificant quantities of conjugate were found after i.v. α-methyldopa. The average fall in mean arterial pressure was 27 mm Hg following i.v. α-methyldopa but only 2.7 mm Hg following α-methyldopate. These results suggest that sulphate conjugation of α-methyldopa occurs in the gastrointestinal tract during absorption. Hydrolysis of α-methyldopa ethyl ester does not appear to be instantaneous and pharmacokinetic differences between the ester and free α-methyldopa have been demonstrated.

Key words

α-methyldopaplasma concentrationhypertensionsulphate conjugation

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • J. A. Saavedra
    • 1
  • J. L. Reid
    • 1
  • W. Jordan
    • 1
  • M. D. Rawlins
    • 1
  • C. T. Dollery
    • 1
  1. 1.M.R.C. Clinical Pharmacology Research Group, Department of Clinical PharmacologyRoyal Postgraduate Medical SchoolLondonU.K.