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ABSTRACT: The study aimed to assess the pharmacokinetics of a new, modified-release metoclopramide tablet, and compare it to an immediate-release tablet. A single and multiple-dose, randomized, open-label, parallel, pharmacokinetic study was conducted. Investigational products were administered to 26 healthy Hispanic Mexican male volunteers for two consecutive days: either one 30 mg modified-release tablet every 24 h, or one 10 mg immediate-release tablet every 8 h. Blood samples were collected after the first and last doses of metoclopramide. Plasma metoclopramide concentrations were determined by high-performance liquid chromatography. Safety and tolerability were assessed through vital signs measurements, clinical evaluations, and spontaneous reports from study subjects. All 26 subjects were included in the analyses [mean (SD) age: 27 (8) years, range 18-50; BMI: 23.65 (2.22) kg/m(2), range 18.01-27.47)]. Peak plasmatic concentrations were not statistically different with both formulations, but occurred significantly later (p < 0.05) with the modified-release form [tmax: 3.15 (1.28) vs. 0.85 (0.32) h and tmax-ss: 2.92 (1.19) vs. 1.04 (0.43) h]. There was no difference noted in the average plasma concentrations [Cavgτ: 23.90 (7.90) vs. 20.64 (7.43) ng/mL after the first dose; and Cavg-ss: 31.14 (9.64) vs. 35.59 (12.29) ng/mL after the last dose, (p > 0.05)]. One adverse event was reported in the test group (diarrhea), and one in the reference group (headache). This study suggests that the 30 mg modified-release metoclopramide tablets show features compatible with slow-release formulations when compared to immediate-release tablets, and is suitable for once-a-day administration.
European Journal of Drug Metabolism and Pharmacokinetics 02/2012; · 0.36 Impact Factor
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ABSTRACT: As intramuscular progesterone administration is associated with local intolerance, the purpose of this work was to determine the local tolerability of a new progesterone microsphere suspension, administered by intramuscular injection.
An observational, longitudinal, prospective, analytical, multicenter, active pharmacovigilance study was conducted. Two hundred and seven progesterone microsphere administrations were evaluated. Patients evaluated pain, burning sensation, pruritus and dysesthesia. Physicians evaluated erythema, pallor, petechia, ecchymosis, bleeding, edema, induration, abscess, macule, papule, vesicle and pustule. Local tolerability was evaluated using a visual analog scale (100-mm line) on the day of administration, and subsequently on days 3 and 7. Local symptoms were evaluated by patients and local signs by the attending physicians.
On the day of application, 68.4% of the administered doses were associated with 'absent' or 'mild' pain, rising to 91.2% on the 7th day; 83.0% of doses were associated with 'absence' of or a 'mild' burning sensation on the day of administration, rising to 99.5% on day 7. On administration day, 13.2% reported 'mild' erythema and 1.0% 'moderate' erythema, and 3.9% of doses had 'mild' induration and 0.5% 'moderate' induration, which increased to 16.6 and 2.9% on day 3, respectively. The values for pallor, ecchymosis, bleeding, edema and pustule were lower than 10 mm (of 100 mm) on the application day and behaved similarly in subsequent days. There were no reports of petechia, abscess, macule, papule or vesicle with the dose application.
Progesterone microspheres were well tolerated without serious or unexpected adverse effects.
Gynecologic and Obstetric Investigation 10/2011; 73(2):124-9. · 1.28 Impact Factor
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ABSTRACT: Metoclopramide is a prokinetic and antiemetic agent.
The goal of this study was to assess the pharmacokinetics of a new, modified-release metoclopramide tablet and compare it with an immediate-release tablet to obtain marketing approval from the Mexican regulatory agency.
This was a single-center, randomized, open-label, parallel-group, single- and multiple-dose, pharmacokinetic study. Investigational products were administered to healthy Mexican male volunteers for 3 consecutive days: one 15-mg modified-release tablet every 12 hours or one 10-mg immediate-release tablet every 8 hours. Multiple blood samples were collected after the first and last doses of metoclopramide over a 24-hour period. Plasma metoclopramide concentrations were determined by using a validated HPLC method. Safety and tolerability were assessed by measurement of vital signs, clinical evaluations, and spontaneous reports from study subjects.
All 26 subjects were included in the analyses (mean [SD] age: 25 [6] years [range, 18-40 years]; body mass index, 23.44 [2.31] kg/m(2) [range, 18.26-27.49 kg/m2]). Peak plasma concentrations were lower (C(max), 33.13 [7.25] vs 46.04 [17.27] ng/mL after the first dose [P < 0.05]; C(max,ss), 48.60 [8.52] vs 75.23 [21.27] ng/mL after the last dose [P < 0.05]) and occurred later (P < 0.05) with the modified-release formulation. In terms of average plasma concentrations (C(avgτ), 20.98 [3.94] vs 23.38 [7.35] ng/mL after the first dose; C(avg,ss), 22.20 [5.64] vs 23.02 [7.77] ng/mL after the last dose), differences did not reach the level of statistical significance (P > 0.05). Four adverse events were reported in the test group (abdominal distention [n = 2], epigastric pain [n = 1], and somnolence [n = 1]), and 3 were reported in the reference group (epigastric pain [n = 1], diarrhea [n = 1], and hiccups [n = 1]).
This study in a sample of selected healthy Mexican male volunteers suggests that the metoclopramide15-mg modified-release tablets have features compatible with the slow-release formulation (lower C(max) and longer T(max)) compared with immediate-release tablets.
Clinical Therapeutics 05/2011; 33(5):630-43. · 2.32 Impact Factor
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ABSTRACT: Trimethoprim/sulfamethoxazole (TMP/SMX) is a combination of 2 antimicrobial agents that act synergistically, sequentially blocking 2 chemical reactions essential to bacterial survival. TMP/SMX is effective against organisms that are resistant to its separate components.
The objective of this study was to compare the bioavailability of 2 commercial preparations of T:MP/SMX 40/200 mg per 5-ml, oral suspension, used in Mexico for the treatment of bacterial infection.
This study used a single-dose, randomized,single-blind, 2 x 2 crossover (2 dosing periods x 2 treatments) design to compare the 2 preparations. Healthy male volunteers aged 18 to 55 years received the trial and reference preparations in randomized sequence, under fasting conditions, with a 7-day washout period between dosing periods. Each preparation was administered as a single-dose 10-ml, oral suspension delivering 80 tng of TMP and 400 mg of SMX (equivalent to 2 doses of TMP/SMX 40/200 rig per 5 ml.). Pharmacokinetic (PK) parameters of C(max) AUC(0-t), and AUC(0-1) were determined for each component of each preparation. Schuirmann's unilateral double t test was performed. Null hypotheses indicating bioin-equivalence (P > 0.05) were rejected. Bioequivalence was determined if the quotient of the parameters of C(max), AUC(0-t), and AUC(0-infinity) were between 80% and 125%, at a power of 80% (alpha > 0.08).
Twenty-three of the 24 enrolled subjects completed the study. The subjects were all Hispanic, the mean (SD) age was 25 (6) years, and the mean (SD) body mass index was 22.54 (2.59) kg/m(2). Plasma concentration-time values of TMP and SMX were similar with both preparations. The null hypotheses of Schuirmann's unilateral double t test were rejected, and results of the analyses of the PK parameters obtained 95% CIs within the predetermined range of bioequivalence (80%-125 degrees 10). The trial and reference preparations were statistically interchangeable and appeared to be bioequivalent.
Based on similar PK profiles and statistical analyses, the trial and reference preparations were statistically interchangeable and appeared to be bioequivalent in this population of 23 healthy male volunteers in Mexico.
Clinical Therapeutics 03/2007; 29(2):326-33. · 2.32 Impact Factor
