Summary
The pharmacokinetics of 2-14C-L-α-methyldopa have been investigated in five healthy volunteers following intravenous and oral administration. In the intravenous study a bi-phasic plasma concentration curve was found both for chemically determined α-methyldopa and for radioactivity. The plasma level of radioactivity differed significantly from chemically determined drug, a pattern which was also found in urine. This suggests the presence of unidentified metabolite(s). The difference between plasma disappearance and urine recovery of α-methyldopa and radioactivity during the first 4 h after injection suggests distribution to an extravascular compartment. Plasma half-lives of total radioactivity and of unchanged drug were calculated. In three subjects, pharmacokinetic parameters for a two-compartment open body model were calculated from urine and plasma data. Urinary recovery of radioactivity was almost complete within 48 h after intravenous administration. After oral administration, however, only about 40 per cent of the radioactive dose was recovered in the urine, and it contained approximately equal amounts of unconjugated methyldopa, acid-labile conjugated methyldopa and unidentified metabolite(s). The acid-labile conjugate was found only after oral administration, which supports the theory of a mucosal conjugation process. The lack of acid-labile conjugated drug either in the plasma or urine after intravenous injection indicates that there is no enterohepatic circulation of this drug.
Similar content being viewed by others
References
Myhre, E., Brodwall, E. K., Stenbæk, Ø., Hansen, T.: Plasma turnover of methyldopa in advanced renal failure. Acta med. scand.191, 343–347 (1972)
Myhre, E., Brodwall, E. K., Stenbæk, Ø., Hansen, T.: The renal excretion of methyldopa. Scand. J. clin. Lab. Invest.29, 201–204 (1972)
Buhs, R. P., Beck, J. L., Speth, O. C., Smith, J. L., Trenner, N. R., Cannon, P. J., Laragh, J. H.: The metabolism of methyldopa in hypertensive human subjects. J. Pharmacol. exp. Ther.143, 205–214 (1964)
Myhre, E., Stenbæk, Ø., Brodwall, E. K., Hansen, T.: Conjugation of methyldopa in renal failure. Scand. J. clin. Lab. Invest.29, 195–199 (1972)
Saavedra, J. A., Reid, J. L., Jordan, W., Rawlins, M. D., Dollery, C. T.: Plasma concentration of α-methyldopa and sulphate conjugate after oral administration of methyldopa and intravenous administration of methyldopa and methyldopa hydrochloride ethyl ester. Europ. J. clin. Pharmacol.8, 381–386 (1975)
Sjoerdsma, A., Vendsalu, A., Engelman, K.: Studies on the metabolism and mechanism of action of methyldopa. Circulation28, 492–502 (1963)
Greenblatt, D. J., Koch-Weser, J.: Clinical Pharmacokinetics. New Engl. J. Med.293/14, 702–705 (1975)
Dollery, C. T., Harington, M.: Methyldopa in hypertension, clinical and pharmacological studies. Lancet1962 I, 759–763
Schrader, K., Brass, H., Renner, D.: Zur Pharmakokinetik von α-Methyldopa bei Niereninsuffizienz. Klin. Wschr.49, 1329–1334 (1971)
Jain, A. K., Ryan, J. R., McMahon, F. G.: The effect of single morning doses of alpha methyldopa (MDo) on blood pressure. Clin. Pharmacol. Ther.14, 137–138 (1973)
Prescott, L. F., Buhs, R. P., Beattie, J. O., Speth, O. C., Trenner, N. R., Lasagna, L.: Combined clinical and metabolic study of the effects of alpha-methyldopa on hypertensive patients. Circulation34, 308–321 (1966)
Stenbæk, Ø., Myhre, E., Brodwall, E. K., Hansen, T.: Hypotensive effect of methyldopa in renal failure associated with hypertension. Acta med. scand.191, 333–337 (1972)
Au, W. Y. W., Dring, L. G., Grahame-Smith, D. G., Isaac, P., Williams, R. T.: The metabolism of14C-labelled α-methyldopa in normal and hypertensive human subjects. Biochem. J.129, 1–10 (1972)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stenbæk, Ø., Myhre, E., Rugstad, H.E. et al. Pharmacokinetics of methyldopa in healthy man. Eur J Clin Pharmacol 12, 117–123 (1977). https://doi.org/10.1007/BF00645132
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00645132