Single dose bioequivalence study of α-methyldopa tablet formulations using a modified HPLC method

Abstract

Background and objective:

The purpose of the present study was to compare the bioavailability of a new methyldopa (CAS 555-30-6) tablet formulation with that of a reference formulation in 12 healthy male subjects using a modified HPLCmethod.

Methods:

The study was designed as anopen label, single-dose, randomizedstudy with a cross-over design. Underfasting conditions, each subject receivedone 250-mg tablet orally as a single doseof a test or reference formulation on twotreatment days. The treatment periodswere separated by a one-week washoutperiod. The blood samples were collectedat different time points after each administration and determined using a rapid and reliable modified HPLC method. Themethod used was validated for specificity, accuracy, precision and sensitivity. The pharmacokinetic parameters (C_max, AUC_0–t, AUC_0–∞ were statistically compared by analysis of variance (ANOVA) fortest and reference formulations.

Results and discussion:

All validationcriteria for the developed HPLC methodwere in acceptable range. The maximumplasma concentration (C_max) of α-methyldopa was 270.3–1864.9 ng/ml for thetest and 224.5 –1585.6 ng/ml for the reference formulation. The mean AUC_0–∞ ofα -methyldopa was 2002.1 –10 614.8 and2076.8–9056.3 ng · h/ml for the test and reference formulation, respectively. Thecalculated 90% confidence intervals for the mean test/reference ratios of mentioned parameters were 92.48–115.94, and 88.82–101.13 which are in the bioequivalence range. The statistical testsdid not show any statistical differencesbetween formulations suggesting thatmethyldopa tablet of test and referencecan be considered as bioequivalent preparations.

Conclusion:

A rapid and reliable HPLCmethod with fluorescence detector wasdeveloped to analyze α-methyldopa inhuman plasma. Based on the obtainedresults the test formulation of α-methyldopa is bioequivalent to the referenceformulation.

Key words

CAS 555-30-6 - Centrally acting antihypertensive agent - α-Methyldopa, bioavailability, bioequivalence, HPLC, pharmacokinetics

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