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British Journal of Clinical Pharmacology Nov 19791 The nine infants participating in this study were born to mothers who received continuous therapy with alpha-methyldopa (0.75-2.0 g/day) for several weeks extending to...
1 The nine infants participating in this study were born to mothers who received continuous therapy with alpha-methyldopa (0.75-2.0 g/day) for several weeks extending to the time of delivery. 2 The concentration of free and total (free plus conjugated) alpha-methyldopa was determined by gas chromatography-mass spectrometry in amniotic fluid, umbilical cord plasma and maternal plasma at delivery; also in urine collected over time intervals from neonates during the first days after birth. 3 The results indicate that alpha-methyldopa administered to the mother is present in the infant at birth at a level comparable to the maternal level and persists for some days. The ratio of conjugated to free drug increases with time after birth. 4 The excretion of free and conjugated alpha-methyldopa in the urine indicated that the drug is slowly eliminated in the neonate by excretion in the urine and apparently by metabolism, mainly to the sulphate conjugate. 5 The concentration of free and conjugated alpha-methyldopa in amniotic fluid tended to be higher than in umbilical cord plasma but lower than in neonatal urine, conjugated drug predominated.
Topics: Amniotic Fluid; Female; Fetal Blood; Humans; Hypertension; Infant, Newborn; Male; Methyldopa; Pregnancy; Pregnancy Complications, Cardiovascular; Time Factors
PubMed: 508547
DOI: 10.1111/j.1365-2125.1979.tb01022.x -
The New England Journal of Medicine May 1976
Topics: Adult; Anxiety; Dementia; Drug Synergism; Haloperidol; Humans; Hypertension; Male; Methyldopa; Middle Aged
PubMed: 1264138
DOI: 10.1056/NEJM197605272942208 -
The Medical Journal of Australia Oct 1966
Topics: Aged; Anemia, Hemolytic; Female; Humans; Methyldopa
PubMed: 5924386
DOI: 10.5694/j.1326-5377.1966.tb97448.x -
The Journal of Pharmacy and Pharmacology Nov 1986An open crossover study of the absorption of alpha-methyldopa has been conducted in normal healthy adult male volunteers in whom a triple lumen perfusion tube had been...
An open crossover study of the absorption of alpha-methyldopa has been conducted in normal healthy adult male volunteers in whom a triple lumen perfusion tube had been placed. Three volunteers were perfused on separate occasions with 0.1 mM alpha-methyldopa at pH 4.5, 6.0 and 7.4. Three other volunteers were perfused on separate occasions with 0.1, 1.0 and 10 mM alpha-methyldopa at pH 6.0. Two additional subjects were perfused with 0.1 mM alpha-methyldopa at pH 6.0. Absorption was not a linear function of concentration above 1 mM alpha-methyldopa. There was also a weak trend toward greater absorption near pH 6.0. At higher concentrations of drug in the perfusion solution (10 vs 1 mM), the free fraction of alpha-methyldopa in plasma samples was increased significantly. Thus, although absorption of alpha-methyldopa is more efficient at lower concentrations, bioavailability may not be substantially enhanced due to increased sulphation in the gut wall. Comparison of permeabilities with previous results from our laboratories suggests the rat is a good model for predicting the behaviour of alpha-methyldopa after its oral administration to man.
Topics: Adult; Body Water; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Kinetics; Male; Methyldopa; Middle Aged; Permeability
PubMed: 2879011
DOI: 10.1111/j.2042-7158.1986.tb04501.x -
The Biochemical Journal Aug 19721. The fate of orally administered (14)C-labelled l-alpha-methyldopa has been examined in three normal men and in eight hypertensive patients who responded to the drug...
1. The fate of orally administered (14)C-labelled l-alpha-methyldopa has been examined in three normal men and in eight hypertensive patients who responded to the drug and three who did not. 2. The output of (14)C in the urine in 2 days and in the faeces in 4 days was not very different in any of the subjects. The normals excreted about 40% of the dose in the urine and 60% in the faeces, the responders 52% (range 35-60%) and 45% and the non-responders 42% and 41%. Most of the urinary (14)C radioactivity was eliminated in 24h after dosing. 3. The main metabolite in the urine was free and conjugated alpha-methyldopa (normal men, 23%; responders, 37%; non-responders, 25% of the dose). Free and conjugated 3-O-methyl-alpha-methyldopa was about 4% in all subjects, total amines (alpha-methyldopamine and 3-O-methyl-alpha-methyldopamine) about 6% and ketones (mainly 3,4-dihydroxyphenylacetone) about 3%. 4. The output of alpha-methyldopamine (2-4% of dose), 3-O-methyl-alpha-methyldopamine (0.3%) and 3,4-dihydroxyphenylacetone (3-5%) was similar in the one normal and two responders examined. 5. The faecal (14)C in all subjects was unchanged l-alpha-methyldopa. 6. In general, the amounts of the metabolites in the urine in normal men and in responding and non-responding patients were quantitatively similar, except in one non-responding patient who converted nearly two-thirds of the absorbed drug into amines and ketones. There appeared to be no correlation between metabolites in the urine and response or lack of response to the drug. 7. In two normal subjects 70-80% of d-alpha-methyldopa was excreted unchanged in the faeces. Of the absorbed compound most (9-14% of the dose) was excreted as the free and conjugated drug together with a small amount (1-2%) of 3-O-methyl-alpha-methyldopa. No amines and only traces of ketone were excreted.
Topics: Adult; Carbon Isotopes; Chromatography, Paper; Chromatography, Thin Layer; Dopamine; Feces; Female; Humans; Hypertension; Ketones; Male; Mass Spectrometry; Methylation; Methyldopa; Middle Aged; Phenylacetates
PubMed: 4646774
DOI: 10.1042/bj1290001 -
Journal of Medicinal Chemistry May 1974
Topics: Animals; Antihypertensive Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Kidney Cortex; Methyldopa; Structure-Activity Relationship; Swine
PubMed: 4830265
DOI: 10.1021/jm00251a029 -
Annals of Internal Medicine Nov 1974
Topics: Biopsy; Drug Eruptions; Fever; Granuloma; Humans; Hypertension; Male; Methyldopa; Middle Aged; Skin
PubMed: 4278641
DOI: 10.7326/0003-4819-81-5-701 -
Postgraduate Medical Journal Jan 1968
Topics: Female; Hemolysis; Humans; Hypertension; Male; Methyldopa; Middle Aged; Pregnancy
PubMed: 5639232
DOI: 10.1136/pgmj.44.507.66 -
British Medical Journal Apr 1977
Topics: Aged; Anemia, Hemolytic; Female; Humans; Liver Cirrhosis; Methyldopa; Psoriasis
PubMed: 851765
DOI: 10.1136/bmj.1.6065.879 -
British Medical Journal May 1976
Topics: Aged; Humans; Hypertension; Male; Methyldopa; Substance Withdrawal Syndrome
PubMed: 1268550
DOI: 10.1136/bmj.1.6017.1056