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Journal of Clinical Pharmacology May 1992A retrospective analysis of previous studies examining methyldopa absorption suggested the possibility that the absorption of methyldopa might increase on repeat...
A retrospective analysis of previous studies examining methyldopa absorption suggested the possibility that the absorption of methyldopa might increase on repeat methyldopa ingestion. A prospective study was undertaken to determine the effect of repeated oral doses of methyldopa on methyldopa absorption. Thirteen healthy subjects ingested single 250 mg methyldopa doses on days 0, 7, 14, 28, 56, and 112; 24 urine samples were collected and analyzed for methyldopa and its major metabolites on each study day and methyldopa plasma levels were measured over 8 hours at days 0 and 56. There were significant increases in the absorption of methyldopa (as estimated by the urinary excretion of methyldopa and the measured metabolites over 24 hours) at day 56 (33.4 +/- 8.9%, P less than .025) compared with day 0 (26.0 +/- 10.8%). There was also a significant increase in renal clearance of unmetabolized methyldopa (62.7 +/- 13.6 vs. 99.3 +/- 29.1 mL/min, P less than .01) and a decrease in the plasma half-life of methyldopa at day 56 (2.22 +/- 0.91 vs. 1.56 +/- 0.68 hr, P less than .05). There was a tendency toward increases in methyldopa absorption at day 7, 14, 28, and 112. Several possible explanations for the changes in methyldopa disposition are discussed.
Topics: Adult; Drug Administration Schedule; Female; Humans; Intestinal Absorption; Male; Methyldopa; Prospective Studies; Retrospective Studies
PubMed: 1587963
DOI: 10.1002/j.1552-4604.1992.tb03861.x -
Journal of Cardiovascular Pharmacology 1981Tolerability data recorded during long-term administration of methyldopa are presented here. Since diuretics and other antihypertensive agents were frequently... (Clinical Trial)
Clinical Trial
Tolerability data recorded during long-term administration of methyldopa are presented here. Since diuretics and other antihypertensive agents were frequently coadministered with methyldopa, no attempt was made to assign possible drug relationships for any particular adverse effect. The most common clinical adverse effects among the entire study population were drowsiness and dizziness. Impotence was reported by 16% of 258 men.
Topics: Adolescent; Adult; Aged; Blood Urea Nitrogen; Clinical Trials as Topic; Creatinine; Diuretics; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Methyldopa; Middle Aged; Retrospective Studies
PubMed: 6172672
DOI: No ID Found -
American Journal of Obstetrics and... Dec 1993The effects of two antihypertensive drugs, methyldopa and isradipine, on fetal heart rate pattern were analyzed by computerized cardiotocography. (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
OBJECTIVE
The effects of two antihypertensive drugs, methyldopa and isradipine, on fetal heart rate pattern were analyzed by computerized cardiotocography.
STUDY DESIGN
The first part of the study was a prospective, randomized, controlled trial of 19 women with preeclampsia in the third trimester given 2.5 mg of oral slow-release isradipine twice a day or 250 mg of methyldopa three times a day. In a second part of the study 23 women with preeclampsia in the third trimester given 5 mg of oral slow-release isradipine twice a day were compared with 23 matched controls without medication. Main outcome measures were maternal blood pressure and mean baseline fetal heart rate, fetal movements, number of accelerations, periods of high and low baseline variability, and mean baseline heart rate variability.
RESULTS
Compared with the pretreatment value, the mean arterial blood pressure decreased significantly in all drug treatment groups. Fetal heart rate characteristics were not significantly changed during drug treatment or bed rest.
CONCLUSION
The various features of the fetal heart rate pattern evaluated by computerized methods were not influenced by treatment with methyldopa or isradipine.
Topics: Adolescent; Adult; Cardiotocography; Female; Heart Rate, Fetal; Humans; Isradipine; Methyldopa; Pre-Eclampsia; Pregnancy; Prospective Studies; Signal Processing, Computer-Assisted
PubMed: 8267066
DOI: 10.1016/0002-9378(93)90440-t -
British Journal of Clinical Pharmacology Jul 1983The absorption and elimination of a single 500 mg dose of methyldopa has been studied after oral administration to 10 normal volunteers, 10 patients with coeliac...
The absorption and elimination of a single 500 mg dose of methyldopa has been studied after oral administration to 10 normal volunteers, 10 patients with coeliac disease, who were on a gluten-free diet, and to five patients with Crohn's disease. In patients with Crohn's disease the percentage of the dose recovered in urine (24%) was about one-half of normal (50%). This decreased absorption was associated with reduced plasma concentrations of both free and conjugated methyldopa and a decreased pharmacological response. In patients with coeliac disease the percentage of dose recovered in urine (43%) was similar to normals, indicating a normal absorption of the drug. However, the plasma concentrations of both free and conjugated methyldopa were significantly higher than normal, although there was no increase in drug-related effects. These findings confirm the importance of using indices other than drug plasma concentrations in the assessment of bioavailability in disease states.
Topics: Adult; Aged; Biological Availability; Biotransformation; Celiac Disease; Crohn Disease; Female; Half-Life; Humans; Intestinal Absorption; Male; Methyldopa; Middle Aged
PubMed: 6882626
DOI: 10.1111/j.1365-2125.1983.tb02147.x -
Journal of the South Carolina Medical... Feb 1989
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Methyldopa
PubMed: 2918712
DOI: No ID Found -
British Medical Journal Jul 1974
Topics: Biopsy; Drug Eruptions; Female; Humans; Hypertension; Lichen Planus; Methyldopa; Middle Aged; Skin
PubMed: 4276925
DOI: 10.1136/bmj.3.5925.234 -
The Journal of Pharmacy and Pharmacology Mar 1996Two dipeptide mimetic prodrugs, 1 and 2, and two tripeptide mimetic prodrugs, 3 and 4, of L-alpha-methyldopa were evaluated for intestinal absorption by in-situ single... (Comparative Study)
Comparative Study
Two dipeptide mimetic prodrugs, 1 and 2, and two tripeptide mimetic prodrugs, 3 and 4, of L-alpha-methyldopa were evaluated for intestinal absorption by in-situ single pass rat jejunal perfusion studies and by in-vitro uptake experiments in brush-border membrane vesicles (BBMVs) prepared from rat intestine. In the perfusion studies, compound 1 demonstrated a 3.5-fold increase in permeability (Pm* = 2.27) as compared with that of alpha-methyldopa (Pm* = 0.65), indicating that this prodrug was better absorbed in the intestine than its parent drug. Other prodrugs showed no significant improvement in intestinal permeability. The results correlated with the results of BBMV uptake studies. In the presence of an inward proton gradient, compound 1 showed Michaelis-Menton saturable kinetics of BBMV uptake with a low value of K(m) (0.06 +/- 0.13 mM) and a high value of Vmax/K(m)(36.38 nmol (mg protein)-1/30s mM-1) at a low concentration range and a linear uptake at high concentrations with Kd = 0.14 +/- 0.02 mM. Compounds 2 and 3 were mainly taken up in BBMVs via passive diffusion. Compound 4 was taken up in BBMVs basically via the carrier-mediated transport system, while the rate of uptake was much lower than that of compound 1. The uptake of compounds 1 and 4 was significantly inhibited by dipeptides L-Gly-L-Pro and L-Gly-L-Phe, and cephradine, a beta-lactam known to be transported via the dipeptide carrier system, indicating that both compounds were taken up in BBMVs via the H(+)-coupled dipeptide-mediated transport system. In contrast to the complicated uptake profile of alpha-methyldopa, the higher rate of BBMV uptake with less variation demonstrated on compound 1 suggested that the attached nonessential amino acid moiety, D-phenylglycine, is a feasible delivery tool in carrying the parent drug through the intestine.
Topics: Animals; In Vitro Techniques; Intestinal Absorption; Jejunum; Male; Methyldopa; Microvilli; Prodrugs; Rats; Rats, Wistar; Subcellular Fractions
PubMed: 8737052
DOI: 10.1111/j.2042-7158.1996.tb05915.x -
Acta Medica Scandinavica Sep 1972
Topics: Adult; Blood Pressure; Brachial Artery; Cardiac Output; Follow-Up Studies; Heart Rate; Hemodynamics; Humans; Hypertension; Male; Methyldopa; Middle Aged; Oxygen Consumption; Physical Exertion; Posture
PubMed: 5055268
DOI: 10.1111/j.0954-6820.1972.tb04805.x -
British Journal of Pharmacology Oct 19701. The antihypertensive action of methyldopa was investigated in the light of the prevailing false sympathetic neurotransmitter hypothesis of Day & Rand (1963)....
1. The antihypertensive action of methyldopa was investigated in the light of the prevailing false sympathetic neurotransmitter hypothesis of Day & Rand (1963). Immunosympathectomized and normal animals were used for the investigation.2. Methyldopa in a single injection significantly decreased the blood pressure in control hypertensive, immunosympathectomized normotensive, and normal rats. Guanethidine did not decrease the blood pressure of immunosympathectomized rats; it decreased the blood pressure of control and control hypertensive rats.3. The hypotensive effect of methyldopa was not antagonized by adrenoceptor and ganglion blocking agents or by the inhibition of dopamine beta-oxidase.4. High doses of methyldopa produced less hypotension than relatively low doses. This might be due to an antagonism of the hypotensive effect by methylnoradrenaline, which is formed from methyldopa.5. The antihypertensive action of methyldopa could not be correlated with any change in aortic sodium or potassium.6. It is concluded that methyldopa does not exert its hypotensive effect by producing a weakly active false sympathetic neurotransmitter.
Topics: Animals; Blood Pressure; Female; Ganglia, Autonomic; Guanethidine; Heart Rate; Hexamethonium Compounds; Immune Sera; Male; Methyldopa; Nerve Growth Factors; Phenoxybenzamine; Potassium; Propranolol; Rats; Sodium; Sympathetic Nervous System
PubMed: 5492891
DOI: 10.1111/j.1476-5381.1970.tb09912.x -
British Journal of Obstetrics and... Jun 1977A total of 242 women with moderate hypertension in pregnancy completed a controlled trial of methyldopa (Aldomet). The hypotensive effect of methyldopa was similar to... (Clinical Trial)
Clinical Trial
A total of 242 women with moderate hypertension in pregnancy completed a controlled trial of methyldopa (Aldomet). The hypotensive effect of methyldopa was similar to its action in non-pregnant individuals and greatly reduced the frequency of severe hypertension occurring antenatally and in labour. As pregnancy advanced, an increasing daily dose of methyldopa was needed and there was a greater use of additional hypotensive therapy. Seventeen (14-5 per cent) women assigned to methyldopa had to be transferred to another drug or had to stop treatment completely because of minor side effects, of which the commonest were lack of energy and dizziness. No serious side effects were encountered. Nine per cent of the untreated women developed severe hypertension which required treatment later in their pregnancies. Six weeks after delivery, nearly all the patients were able to stop treatment.
Topics: Blood Pressure; Clinical Trials as Topic; Female; Humans; Hypertension; Methyldopa; Pregnancy; Pregnancy Complications, Cardiovascular
PubMed: 329859
DOI: 10.1111/j.1471-0528.1977.tb12616.x