Pharmacokinetics and comparative bioavailability of two fenofibrate capsule formulations in healthy volunteers

The objective of this study was to evaluate the pharmacokinetics of fenofibric acid, the main metabolite of fenofibrate (CAS 49562-28-9), and to assess the average bioequivalence of two immediate release formulations of 200 mg fenofibrate capsules in 24 healthy volunteers. The relative bioavailability of the test (generic) product Lipivim with respect to the reference product was determined in a single dose, randomized, crossover study. Only the concentrations of fenofibric acid could be used for bioequivalence determination, because the concentrations of the parent drug were too low to be accurately measured in the biological matrix. The mean values for the Cmax were 3.08 (+/- 1.69) microg/ml for the test and 3.05 (+/- 1.79) microg/ml for the reference product. The mean values for the AUC(0-infinity) were 94.5 (+/- 41.5) microg/ml h for the test and 88.2 (+/- 41.4) microg/ml h for thereference, respectively. The 90% confidence intervals for test/reference mean ratios of the plasma pharmacokinetic variables Cmax, AUC(0-t) and AUC(0-infinity) lie within the conventional bioequivalence range of 80-125% (Schuirman test). The difference between Tmax of the test and reference products was statistically non-significant (Friedman test). The test product is therefore bioequivalent to the reference product with respect to the rate and extent of fenofibric acid pharmacokinetics.     

Pharmacokinetics and comparative bioavailability of two terbinafine hydrochloride formulations after single-dose administration in Chinese healthy subjects

The bioavailability of a new terbinafine (CAS 91161-71-6) preparation was compared with a commercially available original preparation (reference) of the drug in 19 Chinese healthy male volunteers. The study was performed in an open, randomized, single blind two-sequence, two-period crossover design. Under fasting conditions, each subject received a single oral dose of 250 mg terbinafine as a test or reference formulation with a 7-day washout period between the two preparations. The plasma concentrations of terbinafine were analyzed by a sensitive liquid chromatography-ultraviolet spectrometry method. The pharmacokinetic parameters included AUC(0-t) AUC(0-infinity), C(max), t1/2, and T(max). The values of AUC(0-t) demonstrated nearly identical bioavailability of terbinafine from the examined formulations. The AUC(0.48) of terbinafine was 5982.85 +/- 2449.17 and 6761.63 +/- 3140.33 ng x h/ml for the test and reference formulation, respectively. The maximum plasma concentration (C(max)) of terbinafine was 1656.25 +/- 623.18 ng/ml for the test and 1552.07 +/- 660.35 ng/ml for the reference product, respectively. No statistical differences were observed for C(max) and the area under the plasma concentration time curve for terbinafine. The 90% confidence limits calculated for C(max) and AUC from zero to infinity (AUC(0-infinity)) of terbinafine were within the bioequivalence range (80%-125% for AUC). This study shows that the test formulation is bioequivalent to the reference formulation of terbinafine.     

Pharmacokinetics and bioavailability of cyclophosphamide from oral formulations

The bioavailability of three administration forms of cyclophosphamide (CP) was determined by comparison with the i.v. application in 12 female patients with breast cancer. CP charges were given on four consecutive days at a dosage of 175 mg/m2 (50-mg dragees) in a randomized sequence. CP blood levels were measured with N/P flame ionization gas chromatography. The average half-life of intravenously applicated CP and for all three oral formulations was about 4 h. The ratio AUC p.o./AUC i.v. was 0.896 with the gastric juice-resistant formulation of CP, and 0.914 and 0.958 with the two "rapid release" formulations (soluble in gastric juice). The slight differences in the bioavailability and in the peak concentration (19.1; 22.1; 22.8 nmol/ml) were not significant. However, the gastric juice-resistant formulation displayed delayed peak times (2.5 h as compared to 1.13 and 1.42 h) as well as an irregular absorption phase with several maxima in the blood level curves in a few patients. When a first-pass effect of approximatively 8% is added to the bioavailability of the nonmetabolized CP, an almost complete absorption results for all CP formulations. Since the first-pass effect by hepatic metabolism of CP represents no detoxication, but a conversion of inactive CP into the actual cytostatically active form, a cytostatic bioavailability of likewise almost 100% can also be assumed.     

Comparative bioavailability of two oral formulations of bromazepam in healthy volunteers.

The aim of this study was to assess the pharmacokinetic profile of two bromazepam (CAS 1812-30-2) formulations in 24 healthy volunteers. An open, randomised clinical trial designed as two-period crossover with 14-day washout between doses was employed. Plasma samples for assessments of their bromazepam concentration by HPLC-UV were obtained over 96 h after administration. No adverse effect was reported for any of the formulations administered. The following pharmacokinetics parameters were calculated: AUC(0-96 h), AUCinf, Cmax, Tmax, Ke and T1/2. The 90% confidence intervals (CI) for the mean test/reference individual ratios were 81-109 for AUC and 84-116 for Cmax. Since the 90% CI for both, AUC and Cmax ratios were within the 80-125% interval proposed by the Food and Drug Administration, it is concluded that the new bromazepam slow-release formulation is therapeutic equivalent to the conventional formulation for both, the extent and the rate of absorption after single dose administration in healthy volunteers.     

Comparative bioavailability study of two oral omeprazole formulations after single and repeated administrations in healthy volunteers

OBJECTIVE: Two oral enteric-coated pellet formulations of omeprazole, Pepticum((R)) (test formulation) and Mopral((R)) (reference), were administered to 24 healthy volunteers for 5 days at a daily dose of 20mg omeprazole in order to investigate the comparative bioavailability of the two formulations. RESULTS: The data obtained in this study demonstrated the bioequivalence of the two formulations. No statistical differences were observed for the area under the plasma concentration-time curve (AUC(0-t)), the parameter to which the inhibition of acid secretion induced by omeprazole is directly related. Differences observed in maximum plasma drug concentration (C(max)) at day 1 for both formulations were not statistically significant. At steady-state, the differences found in C(max) were associated with a p-value <0.05 with the 90% confidence interval lying between the acceptance range (70 to 140%). Regarding time to reach C(max) (t(max)), p < 0.01 was found both after single and repeated doses. In both cases, Pepticum((R)) showed a delay in reaching C(max) compared with Mopral((R)): 2.15 +/- 1.11 vs 1.48 +/- 0.52h (day 1) and 1.94 +/- 0.66 vs 1.31 +/- 0.75h (day 5). CONCLUSION: This study confirmed the reported increases in AUC and C(max) after repeated administrations, the important intersubject variability and the excellent biological and clinical tolerability of both formulations.     

Pharmacokinetics and comparative bioavailability of two vinpocetine tablet formulations in healthy volunteers by using the metabolite apovincaminic acid as pharmacokinetic parameter

The objective of this study was to evaluate the pharmacokinetics of apovincaminic acid, the main metabolite of vinpocetine ((3alpha, 16alpha) -eburnamenine-14-carboxylic acid ethyl ester, CAS 42971-09-5), and to assess the average bioequivalence of two immediate release formulations of 10 mg vinpocetine tablets in 24 healthy male volunteers. The relative bioavailability of the test (generic) product (Vimpocetina) with respect to the reference product was determined in a single dose, randomized, crossover study. A simple, rapid specific and reliable high performance liquid chromatographic method coupled with mass spectrometry detection has been developed and validated for vinpocetine and apovincaminic acid. However, only the concentrations of the metabolite could be used for bioequivalence determinations because the concentrations of the parent drug were too low to be accurately measured in the biological matrix. The compartmental analysis of the metabolite's appearance-disappearance in blood shows similarity with first-order kinetics of a drug extravascularly administered. The apparent pharmacokinetic constants were determined. The mean values for the Cmax were 49.5 (+/- 16) ng/ml for test and 51.4 (+/- 14) ng/ml for the reference product. The mean values for the AUC0-infinity were 95 (+/- 29) ng/ml x h for test and 96.9 (+/- 26) ng/ml x h for reference, respectively. The 90 % confidence intervals for test/reference mean ratios of the plasma pharmacokinetic variables Cmax and AUC0-infinity lie between 0.83-1.08 and 0.88-1.08, respectively, which is within the conventional bioequivalence range of 80-125 % (Schuirman test). The difference between Tmax of the test and reference products was statistically non-significant (Friedman test). The test product is therefore bioequivalent to the reference product with respect to the rate and extent of apovincaminic acid pharmacokinetics.     

Comparative bioavailability study with two chlorpropamide tablet formulations in healthy volunteers

OBJECTIVE: The aim of this study was the assessment of the bioequivalence of two formulations (250 mg tablet) of chlorpropamide (CAS 94-20-2) in 36 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 3-week washout interval. Plasma samples were obtained over a 72-h period. Plasma chlorpropamide concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the chlorpropamide plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUC(0-72h), AUC(inf) and C(max). RESULTS: The limit of quantification was 0.1 microg/mL for plasma chlorpropamide analysis. The geometric mean and respective 90 % confidence interval (CI) of Test/ Reference percent ratios were 93.99% (87.11%-101.41%) for C(max), 92.45% (85.96%-99.44%) for AUC(0-72h) and 90.30% (83.35%-97.82%) for AUC(0-inf). CONCLUSION: Since the 90 % CI for AUC(0-72h), AUC(0-inf) and C(max) ratios were within the 80-125%interval proposed by the US FDA, it was concluded that chlorpropamide 250 mg tablet (test formulation) was bioequivalent to the reference 250 mg tablet for of both the rate and extent of absorption.     

Comparative bioavailability study with two gemfibrozil tablet formulations in healthy volunteers

OBJECTIVE: To assess the bioequivalence of gemfibrozil (CAS 25812-30-0) 900 mg tablet formulation from EMS Farmaceutica as test formulation versus a 900 mg tablet formulation as reference in 36 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval. Plasma samples were obtained over a 24-h period. Plasma gemfibrozil concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). From the gemfibrozil plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUClast, AUC(0-inf) and Cmax. RESULTS: The limit of quantification was 0.05 microg/mL for plasma gemfibrozil analysis. The geometric mean and respective 90% confidence interval (CI) of Test/Reference percent ratios were 90.29 (81.39-100.17) for Cmax, 96.26 (90.33-102.59) for AUClast, 96.04 (90.21-102.23) for AUC(0-24 h) and 96.62 (90.82-102.78) for AUC(0-infinity). CONCLUSION: Since the 90% CI for AUClast, AUC(0-inf) and Cmax, ratios were within the 80-125% interval proposed by the U.S. FDA, it was concluded that gemfibrozil 900 mg tablet (test formulation) was bioequivalent to the 900 mg tablet reference formulation for both rate and extent of absorption.     

Pharmacokinetics of methylphenidate after oral administration of two modified-release formulations in healthy adults

OBJECTIVE: To compare the rate and extent of absorption of DL-threo-methylphenidate (MPH) from two modified-release MPH formulations at their respective recommended starting doses in healthy adult volunteers. DESIGN: Open-label, randomised, crossover, bioavailability study. PARTICIPANTS: Twenty healthy adult male and female volunteers. METHODS: Subjects received single doses of two modified-release formulations of MPH, a 20mg capsule (Ritalin) LA) and an 18 mg tablet (Concerta). A total of 19 plasma samples was collected over 24 hours, and MPH plasma concentrations were determined by liquid chromatography-mass spectrometry (LC-MS/MS). These values were used to calculate standard noncompartmental pharmacokinetic parameters describing the rate (peak concentration and time to peak concentration) and extent (area under the concentration-time curve, AUC) of absorption of the two formulations. The relative bioavailability of the two drugs was assessed using a 90% confidence interval, based on the lower and upper endpoints of the confidence interval for the ratios of the geometric means (log transformed) being within the 0.80-1.25 equivalence criterion. RESULTS: Nineteen subjects, ten male and nine female, aged 21-34 years completed both treatment phases of the study. The Ritalin LA formulation displayed a distinctly biphasic pharmacokinetic profile, with mean initial peak plasma concentration of 7 microg/L at an average of 2.1 hours after administration and a second peak of 9.3 microg/L occurring at 5.6 hours. In contrast, the profile of the Concerta formulation rapidly reached an initial plateau concentration of 3.4 microg/L at 3.3 hours after administration and a second mean plateau concentration of 5.9 microg/L approximately 6 hours after administration. Substantially more MPH was absorbed from Ritalin LA than from Concert over the first 4 hours; the respective AUC(4) values were 18.5 and 9.3 microg x h/L (p < 0.001). The overall extent of absorption of MPH was similar between the two formulations. Oral clearance was identical between the two dosage forms. CONCLUSIONS: The Ritalin LA formulation exhibited more rapid initial absorption and reached significantly higher peak plasma concentrations compared with the Concerta formulation, although the oral bioavailability of MPH was similar between the two formulations. The Ritalin LA capsule demonstrated a distinctly bimodal plasma concentration-time profile. MPH plasma concentrations resulting from Concerta reached a peak at 6 hours. These results indicate that the recommended starting dose of the Ritalin LA 20 mg capsule formulation provides more rapid absorption and higher peak plasma concentrations than the recommended 18 mg starting dose of the Concerta formulation.     

Relative bioavailability study of two nifedipine tablet formulations in healthy male volunteers

OBJECTIVE: To assess the bioequivalence of two oral formulations containing 10 mg of nifedipine. The test preparation were Macorel tablets, the reference preparation were Adalat tablets. SUBJECTS, MATERIAL AND METHODS: The study was designed as a single-dose, three-period crossover randomized design to 18 non-smoker, healthy male volunteers under fasting conditions. Seventeen volunteers completed the study. Plasma samples were analyzed for nifedipine by HPLC after solid-phase extraction. The pharmacokinetic parameters used to assess the bioequivalence of the two formulations were AUC(0-infinite) and AUC(0-t) for the extent of absorption and Cmax and Tmax for the rate of absorption. Statistical comparisons of AUC(0-infinite) AUC(0-t), and Cmax data were evaluated after logarithmic transformation by two-way analysis of variance (ANOVA), and differences of Tmax were tested non-parametricaly. RESULTS: Point estimates (90% confidence intervals) of the test/reference ratios were 97.4% (87.6%-108.3%) for AUC(0-infinite) 97.0% (85.6%-110.1%) for AUC0-t, and 107.7% (89.1%-130.7%) for Cmax. No statistically significant difference was found for Tmax and elimination half-life values. CONCLUSION: Therefore, in accordance with the European Union bioequivalence requirements, the test and reference nifedipine preparations are bioequivalent for both the extent and the rate of absorption.     

Comparative bioavailability study of two phenoxymethylpenicillin potassium tablet formulations in healthy volunteers

OBJECTIVE: The aim of this study was to evaluate the performance of 2 phenoxymethylpenicillin 500,000 UI tablet formulations in healthy human volunteers. MATERIAL AND METHODS: The study was conducted using an open, randomized crossover design with a 7-day washout interval. A single dose of each formulation was administered to 26 healthy volunteers as assessed by clinical and laboratory test evaluations. The plasma samples were obtained over an 8-h interval and phenoxymethylpenicillin concentrations were quantified by a suitable and validated HPLC-UV method with detection at 220 nm. Systolic and diastolic blood pressure and pulse rate measurement were taken pre dose and at intervals up to 8 h. RESULTS: Tolerance of both products was adequate. The mean of Meracilina/Pen-Ve-Oral 500,000 UI% geometric mean was 99.89% for AUC0-t, 100.86% for AUC0-infinity and 101.11% for Cmax. The 90% confidence intervals were 94.62 - 105.46%, 95.22 - 106.83% and 98.61 - 103.87%, respectively. The mean recovery of phenoxymethylpenicillin was 94.8%, while the retention time observed for phenoxymethylpenicillin and phenytoin (internal standard) was 4 and 10 min, respectively. The limit of quantification was 0.10 mg/l. CONCLUSION: Since the 90% CI for AUC0-t, AUC0-infinity and Cmax ratios were all within the 80 - 125% interval proposed by the US FDA and accepted by ANVISA, it was concluded that the Meracilina formulation (manufactured by AchA(c) S.A.) is bioequivalent to Pen-Ve-Oral (manufactured by Eurofarma) for both the rate and the extent of bioavailability.     

国产世福素胶囊的人体药代动力学及相对生物利用度研究

健康志愿者１０名，分别ｐｏ２００ｍｍ日本或国产世福素胶囊后，其体内过程符合一室模型，主要药动学参数分别为；Ｃａｘｍ为２．１７±０．３８及２．１７±０．３８ｍｇ·Ｌ－１；Ｔ为３．４５±０．３２及３．６０±０．５２ｈ；Ｔｐ为４．５８±０．５６及４．６２±０．３５ｈ；ＡＵＣ为２６．３５±４．２７及２５．８５±３．８０ｍｇ·ｈ－１．Ｌ－１。国产世福素胶囊与日本产世福素胶囊的相对生物利用度为９９％。血浆药物浓度采用微生物法测定。     

A bioavailability/bioequivalence study of two oral lansoprazole formulations after single administration to healthy volunteers.

Two oral lansoprazole formulations, containing encapsulated microgranules, Lasoprol (test formulation) and Lanzor (reference), were administered to 12 healthy volunteers of both sexes in a single dose of 30 mg lansoprazole in order to investigate their comparative bioavailability. No statistically significant differences, at the probability level of 90%, were observed neither for the maximal serum concentrations (1.12:1.22 micrograms/ml) nor for the area under the concentration-time curves (5.01:5.77 micrograms/ml.h), the parameter to which the inhibition of acid secretion induced by lansoprazole is directly related. The similar holds true for the value of time to reach the maximal concentration of lansoprazole in serum, although this parameter was previously described as less sensitive in comparative bioavailability studies. The terminal elimination half-lives were 4.56 h for Lasoprol and 4.57 h for the reference formulation. The results indicate the bioequivalence and good tolerability of both lansoprazole formulations. The overall pharmacokinetic profile of the drug was comparable with the data previously reported by other investigators.     

Comparative bioavailability of two oral formulations of ranitidine

The current requirement of the Mexican Authorities to demonstrate the interchangeability of ranitidine formulations is to establish that the dissolution profile of the drug shows similarity. In order to establish if this requirement is adequate, the bioavailability of two formulations that did not meet this similarity were compared. Twenty-five female volunteers received 150 mg ranitidine (Azantac or Midaven) under fasting conditions in two separate sessions using a cross-over design. Plasma samples were obtained at selected times for a period of 12 h and stored frozen at -80 degrees C until analysed. Ranitidine plasma levels were determined and pharmacokinetic parameters were obtained. Values (mean+/-SEM) were: Cmax 528.85+/-25.34 and 563.03+/-33.25 ng/ml, tmax 2.76+/-0.19 and 2.79+/-0.18 h, and AUC12 h 2694.94+/-99.50 and 2648.51+/-133.38 ng.h/ml, for Azantac or Midaven, respectively. No statistically significant difference was obtained in the parameters evaluated. Moreover, 90% confidence limits were 96.6%-116.2% and 90.7%-105.1% for Cmax and AUC12 h ratios, respectively, indicating that the formulations tested are bioequivalent, despite the dissimilarity in the dissolution profile of the formulations. These results suggest that the comparative dissolution profile is not an adequate test to demonstrate the interchangeability of ranitidine formulations.     

Cyclosporine bioavailability of two physically different oral formulations

To assess the comparative bioavailability of two cyclosporine capsule products with different pharmaceutical formulation an open randomized two-period cross over study was conducted in 24 healthy volunteers. Our results, obtained from cyclosporine HPLC determination onto the whole blood samples collected, show that the test cyclosporine non-SMEDDS formulation was not bioequivalent cyclosporine SMEDDS formulation due to a statistically significantly lower absorption rate. The outcome does not support free and full interchangeability in chronic stable graft recipients of the two products studied, unless validated clinical and laboratory conversion protocols for each kind of organ transplantation are enforce.     

Comparative bioavailability study of two cefixime formulations administered orally in healthy male volunteers

The bioavailability of a new cefixime ((6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo-[4,2,0]-oct-2-ene-2-carboxylic acid, CAS 79350-37-1) tablet preparation (Loprax) was compared with that of a reference preparation of the drug in 24 healthy male volunteers. The trial was designed as an open, randomized, single-blind, two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 400 mg cefixime tablet as a test or reference formulation on 2 treatment days. The treatment periods were separated by a one-week washout period. The plasma concentrations of the drug were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC0-24h, AUC0-infinity, Cmax, t1/2, and Ke. The mean AUC0-infinity of cefixime was 45008.7 +/- 10989.9 and 45221.3 +/- 2155.7 n x h/ml for the test and reference formulation, respectively. The maximum plasma concentration (Cmax) of cefixime was on average 4746.9 +/- 1284 ng/ml for the test and 4726.3 +/- 1206.9 ng/ml for the reference product. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for test and reference tablets. The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of Cmax, AUC0-infinity and AUC0-24h of cefixime were in the bioequivalence range (94%-112%). Therefore, the two formulations were considered to be bioequivalent.     

Bioequivalence study of two oral formulations of cefadroxil in healthy volunteers

Two different cefadroxil (CAS 50370-12-2) formulations were evaluated for their relative bioavailability in 24 healthy volunteers who received a single 500 mg oral dose of each preparation. An open, randomized clinical trial designed as a two-period crossover study with a 7-day washout period between doses was employed. Plasma samples for assessments of their cefadroxil concentration by HPLC-UV were obtained over 8 h after administration. Values of 48.94 +/- 10.18 pg x h/ml for test, and 48.51 +/- 9.02 microg x h/ml for the reference preparation AUC(0-t) demonstrate a nearly identical extend of drug absorption. Maximum plasma concentration Cmax of 16.04 +/- 4.94 microg/ml and 16.01 + 4.02 microg/ml achieved for the test and reference preparations did not differ significantly. The parametric 90% confidence intervals (CI) of the mean of the difference (test-reference) between log-transformed values of the two formulations were 96.80% to 104.51% and 92.01% to 107.00% for AUC(0-t) and Cmax, respectively. Since for both AUC(0-t) or Cmax the 90% CI values are within the interval proposed by the Food and Drug Administration, the test product is bioequivalent to the reference product for both the rate and extent of absorption after single dose administration.     

Bioavailability study of two oral formulations of didanosine in healthy volunteers

An open-label, randomised, crossover single dose study, using 2 periods, 2 sequences, with a minimum washout period of 7 days, was conducted in order to assess the comparative bioavailability of two formulations of didanosine (CAS 69655-05-6) 100 mg tablets. Didanosine plasma concentrations were determined by means of a validated HPLC method [DAD detector, stavudine (CAS 3056-17-5) as an internal standard]. The limit of detection was 30 ng/ml. The results showed that overall classical 90 % confidence intervals (CI) were 92.4-111.2 % for AUC0-inf, 91.8-109.9 %f for AUC0-t, and 87.0-110.0 % for Cmax. Since the 90 % CI for both, AUC and Cmax ratios were within the 80-125 % interval proposed by the European Agency for the Evalution of Medicinal Products (EMEA) and Food and Drug Administration (FDA), it is concluded that the new didanosine formulation is equivalent to the conventional formulation for both, the extent and the rate of absorption after single dose administration in healthy volunteers.     

Clarithromycin bioequivalence study of two oral formulations in healthy human volunteers

OBJECTIVE: To assess the bioequivalence of two tablet formulations of clarithromycin (Clamicin 500 mg from Medley Indlistria Farmaceutica, Brazil, as the test formulation, and Biaxin 500 mg from Abbott Industries, USA, as the reference formulation). METHODS: A single 500 mg oral dose of each formulation was administrated in 24 healthy volunteers of both sexes (12 males and 12 females). The study was conducted open, randomized, two-period crossover design with a 7-day interval between doses. The plasma concentrations of clarithromycin were quantified by reversed phase liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM) method. 14-hydroxyclarithromycin concentration was estimated semiquantitatively as equivalent of clarithromycin/ml. The precision of the method was evaluated using calibration curves and plasma quality control samples. The pharmacokinetic parameters calculated for both compounds included: AUC(0 - 48h), AUC(0 - infinity), Cmax, Cmax/AUC(0 - 48h), Tmax, T1/2 and Ke. RESULTS: Standard curves of clarithromycin in plasma were linear in the range of 0.05 microg x ml(-1) to 10 microg x ml(-1) (r > 0.999). The limit of quantification was 5 ng/ml. Within- and between-run plasma quality control CV were 5.8% and 15.7%, respectively. Inaccuracy within- and between-runs were 14% and 17%, respectively. 90% CI for clarithromycin geometric mean AUC(0 - 48h), AUC(0 - infinity) and Cmax ratios (test/reference) were: 8.7% - 103.1%, 89.4% - 103.7% and 85.4% - 99.6%, respectively, and for hydroxyclarithomycin were 80.3% - 108.6%, 80.1% - 110.1% and 85.4% - 112.6%, respectively. CONCLUSION: The method described for the quantification of charithomycin and its main metabolite is accurate and sensitive. Clamicin was considered bio-equivalent to Biaxin based on the rate and extent of absorption. Since these were no significant differences in the bioequivalence determined using the pharmacokinetic parameters of either clarithromycin or 14-hydroxyclarithromycin, we suggest that future bioequivalence trials of this drug may be performed by quantifying clarithromycin only.