Concentration and pH dependency of α-methyldopa absorption in rat intestine

Amidon, Gordon L.; Merfeld, Ann E.; Dressman, J.B.

doi:10.1111/j.2042-7158.1986.tb04588.x

Cited by 23 publications

(9 citation statements)

References 17 publications

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“…Each tablet weighing about 600 mg (HPMC 150 000 cps or AAM) was prepared adding 0.5% of magnesium stearate at different compression pressures (10,30,50, 70 and 90 MPa).…”

Section: Study Of Compaction Characteristicsmentioning

confidence: 99%

“…Tablets of methyldopa, a model drug for evaluating the dissolution enhancer performance, were prepared by wet granulation (10). Due to its intense oxidation, we used a PVP K-30 3.0% w/v ethanol:water (70:30) solution, containing 0.1% w/v (relative to the total liquid volume) of sodium metabisuphite as granulation liquid (15).…”

Section: Tablets Formulationmentioning

confidence: 99%

“…On that purpose we studied the functionality of this silicate, the use as precursor for preparation of new nanocomposites (AAM/PVP and AAM/GME) with dissolution enhancer, and the drug release control properties. For the evaluation of these new excipients, two known model drugs were used including methyldopa, which presents low solubility in water (class II of BCS) and high instability due to oxidative processes (10), and theophylline for sustained release experiments due to its physicochemical properties (11). The study also compared the AAM and its nanocomposites with commonly used excipients, including HPMC 150000 cps, sodium lauryl sulphate (surfactant), croscarmellose sodium (superdisintegrant) (12), aerosil (silicates) (13), for different pharmacotechnical purposes.…”

Section: Introductionmentioning

confidence: 99%

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Preparation and Evaluation of a New Nano Pharmaceutical Excipients and drug Delivery System Based in Polyvinylpyrrolidone and Silicates

et al. 2011

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-Purpose. The aim of this work is to prepare new nanocomposites based on a lamellar silicate alkyl ammonium montmorillonite (AAM) obtained by the intercalation of polyvinylpyrrolidone (PVP K-30) and glyceril monostearate (GME). Methods. AAM was characterized by XRD, TGA and DSC analysis and its compactation characteristics, functionality and toxicity were also tested. The AAM/PVP K-30 and AAM/GME nanocomposites were evaluated by XRD diffratograms to measure the interlamellar spacing values in order to prove the new nanocomposites formation. Tablets were prepared using methyldopa and theophylline as model drugs whereas the dissolution tests were carried out in simulated gastric and enteric fluids. Results. AAM showed a good compactability and compressibility characteristics for tablets preparation. The intercalation yields (~ 25%) of the nanocomposites were efficient. The AAM/PVP K-30 nanocomposites were successfully tested as dissolution enhancers and sustained release matrixes. Conclusions. The results suggest to the promising use of AAM (viscogel B8) and to the new nanocomposite prepared by clay/PVP K-30 intercalation as a new matrix for sustained release. These data also point to the feasibility of using these new nanocomposites as dissolution enhancer. __________________________________________________________________________________________

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“…Each tablet weighing about 600 mg (HPMC 150 000 cps or AAM) was prepared adding 0.5% of magnesium stearate at different compression pressures (10,30,50, 70 and 90 MPa).…”

Section: Study Of Compaction Characteristicsmentioning

confidence: 99%

Section: Tablets Formulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preparation and Evaluation of a New Nano Pharmaceutical Excipients and drug Delivery System Based in Polyvinylpyrrolidone and Silicates

et al. 2011

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“…Several drugs such as methyldopa, 1-dopa, digoxin, 5-fluorouracil, methotrexate, penicillins and cephalosporins utilize transporters during absorption and renal excretion [9][10][11][12][13][14][15][16][17][18][19]. Methyldopa is absorbed in part from the gastrointestinal tract by the neutral amino acid transporter [13,14,20].…”

mentioning

confidence: 99%

“…Methyldopa is absorbed in part from the gastrointestinal tract by the neutral amino acid transporter [13,14,20]. As the neutral amino acid transporter in the gastrointestinal tract is regulated by substrate [21,22], methyldopa could cause an increase in gastrointestinal neutral amino acid transporter function during therapy.…”

mentioning

confidence: 99%

Methyldopa kinetics before and after ingestion of methyldopa for eight weeks

Campbell

Robertson

Burgess

et al. 1995

Eur J Clin Pharmacol

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Methyldopa urine and plasma levels and urine metabolite levels were assessed following intravenous (IV) and oral (PO) methyldopa before, and after ingestion of methyldopa (500 mg) daily for eight weeks. There was no increase in (estimated) methyldopa absorption (8.4%) or renal clearance (PO 13.9%, IV 2.33%) after the eight weeks of methyldopa ingestion. However, the initial methyldopa absorption and renal clearance values in this study were higher than that in previous studies. There was an inverse relation between the initial methyldopa absorption and the change in absorption (r - 0.605) and between the initial methyldopa renal clearance and the change in renal clearance (PO r -0.874, IV r -0.891). Overall, this study did not confirm our previous studies showing induction of methyldopa absorption and renal clearance, possibly due to prior up regulation of transporter function. Consistent with methyldopa inducing drug transporters, those with low initial absorption and renal clearance values had the greatest increases.

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Dose‐dependent pharmacokinetics: Experimental observations and theoretical considerations

Lin

1994

Biopharm & Drug Disp

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Clinically, absorption and elimination of most drugs follow linear kinetics, and pharmacokinetic parameters describing absorption and elimination of a drug do not change over the therapeutic dose range. However, dose-dependent pharmacokinetics have been reported more frequently in preclinical studies, particularly in toxicity studies, where high doses are often employed. This review highlights the major types of dose-dependent pharmacokinetics with unique examples.Before setting out on a pivotal subchronic and chronic toxicity study of a new drug, a pilot study is often performed to establish a dose range in which a reasonable relationship between plasma AUC and dosage exists to ensure sufficient exposure of animals to the drug. Theoretical bases and possible causes of dose-AUC disproportionality are discussed.Factors affecting the distribution and elimination of drugs and causes of dose-dependent tissue distribution and elimination are also discussed. Often, the non-linear kinetics complicate the design of dosage regimens and prediction of efficacy and toxicity. Thus, an understanding of the influence of dose on the pharmacokinetics is important in the evaluation of the efficacy and toxicity of new drugs.

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Concentration and pH dependency of α-methyldopa absorption in rat intestine

Cited by 23 publications

References 17 publications

Preparation and Evaluation of a New Nano Pharmaceutical Excipients and drug Delivery System Based in Polyvinylpyrrolidone and Silicates

Preparation and Evaluation of a New Nano Pharmaceutical Excipients and drug Delivery System Based in Polyvinylpyrrolidone and Silicates

Methyldopa kinetics before and after ingestion of methyldopa for eight weeks

Dose‐dependent pharmacokinetics: Experimental observations and theoretical considerations

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