Dataset Information

A Relative Bioavailability Study of Two Misoprostol Formulations Following a Single Oral or Sublingual Administration.

ABSTRACT: Introduction:Misoprostol (Cytotec) was primarily made for treating gastric ulcers. However today it is mostly used for abortion, treating postpartum hemorrhage, and for induction of labor. The tablet contains 200 µg of misoprostol, yet the dosages used for induction of labor are much smaller (25-50 µg), leading to uncertainty of dosage in daily use. Aim:To evaluate and compare the relative bioavailability of two misoprostol products (Angusta 25 µg and Cytotec 200 µg tablets) administered orally or sublingually given in a daily clinical setting to women admitted for induction of labor at term. Methods:Women carrying a live, singleton fetus in a cephalic position and with a gestational age between 259 and 296 days were included. Blood samples were collected at 0, 5, 10, 20, 30, 40, 50, 75, 100, 120, 180, and 240 minutes. A serum analytical assay was performed and pharmacokinetic parameters were calculated. Patients were assigned to one of three groups. Results:A total of 72 patients were included. No significant differences demographic characteristics were found. The ratios for AUC, AUC (0-t), and Cmax were similar in all three groups, but CI-values were outside the required 80-125%. Sublingual administration yielded a 20-30% higher bioavailability and a 50% higher Cmax than compared to the oral route. Conclusion:The relative bioavailability between Angusta and Cytotec could not be confirmed as being equal at the 25 µg or 50 µg level because the 90% CI-values when comparing the ratios for AUC, AUC(0-t), and Cmax were wider than accepted. The reason for this could be the real-life, non-standardized circumstances in which the study was conducted. Sublingual administration seems to have higher bioavailability than oral administration. More studies are needed to ascertain an optimal dosage regime balancing both safety and efficacy for mother and child. Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT02516631.

SUBMITTER: Amini M

PROVIDER: S-EPMC7029744 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Relative Bioavailability Study of Two Misoprostol Formulations Following a Single Oral or Sublingual Administration.

Amini Mahdi M Reis Margareta M Wide-Swensson Dag D

Frontiers in pharmacology 20200212

<h4>Introduction</h4>Misoprostol (Cytotec) was primarily made for treating gastric ulcers. However today it is mostly used for abortion, treating postpartum hemorrhage, and for induction of labor. The tablet contains 200 µg of misoprostol, yet the dosages used for induction of labor are much smaller (25-50 µg), leading to uncertainty of dosage in daily use.<h4>Aim</h4>To evaluate and compare the relative bioavailability of two misoprostol products (Angusta 25 µg and Cytotec 200 µg tablets) admin ...[more]

PMID: 32116725

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Project description:BACKGROUND AND OBJECTIVE: Probiotics are live microorganisms that may provide benefits including the prevention of gastrointestinal disorders and other diseases. Enterogermina is a probiotic mix of spores from four strains of Bacillus clausii (O/C, T, N/R and SIN), available in several oral formulations. The objective of this analysis was to evaluate and compare the kinetic profiles of different formulations of Enterogermina-vial [E4 once daily (OD) and E2 twice daily (BID)], capsule [EC2 three times daily (TID)], oral powder for suspension (ES6 OD) and oral powder not requiring suspension (E6 OD) from two studies from 2012 (EUDRACT 2010-024497-19 and 2010-023187-41) and one study from 2016 (EUDRACT 2015-003330-27).MethodsB. clausii spores were counted in homogenised faecal samples (results expressed as counts per gram) or after culture at 37 °C for 24-36 h (results expressed as colony-forming units). Kinetics were assessed by area under the concentration-time curve (AUC), maximum concentration (Cmax), time to maximum concentration (Tmax) and spore presence/persistence.ResultsIn total, 22 subjects in each of the 2012 studies and 30 subjects in the 2016 study were randomised (mean age 25.0-33.8 years across studies). The mean (±SD) absolute faecal spore counts (in millions) expressed as AUC per hour were 270.7 ± 147.7 (E2 BID) and 213.8 ± 60.2 (E4 OD) in 2012 EGKINETIC4, 312.7 ± 218.0 (EC2 TID) and 319.0 ± 221.1 (ES6 OD) in 2012 EGKINETIC6, and 212.6 ± 118.0 (E6 OD) and 293.2 ± 247.2 (ES6 OD) in 2016 EGKINETIC6OP. The kinetic profiles of the different formulations of Enterogermina were similar, with superimposable AUC and daily curve profiles in each study up to the 8th day post dose. B. clausii spore presence/persistence in the intestine of healthy volunteers did not differ between the two formulations within each of the three studies. Enterogermina was well tolerated across all formulations and studies.ConclusionThese results show different formulations of Enterogermina had similar kinetic profiles within each study; however, they also showed that probiotics could be associated with high variability. The European Medicines Agency guidelines are the current bioequivalence reference, although only the Tmax parameter is used for high variability drugs. Due to the specific kinetics of probiotics, new parameters of bioequivalence could be necessary, considering, for example, variability via a parameter such as AUC.Trial registrationEUDRACT 2010-024497-19, 2010-023187-41 and 2015-003330-27.

Project description:This study aimed to assess and compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties following a single subcutaneous injection of epoetin alfa (Eporon®) with those of the comparator (Eprex®) in healthy male subjects.A randomized, double-blind, two-sequence, crossover study was conducted. Subjects were randomly assigned to receive a single dose, that is, 4,000 IU, of the test or comparator epoetin alfa. After 4 weeks, all subjects received the alternative formulation. The primary PK parameters, maximum observed concentration (Cmax) and area under the curve extrapolated to infinity (AUCinf), were calculated with the serum erythropoietin (EPO) concentrations from blood samples collected for 144 h after dosing. The reticulocyte, hematocrit, hemoglobin and red blood cell counts were measured up to 312 h as PD markers. The primary PD parameters, maximum observed effect (Emax) and area under the effect curve (AUEC), were obtained from the baseline-corrected reticulocyte count. The serum EPO concentration and the reticulocyte count were used to assess the concentration-response relationship. The tolerability and immunogenicity profiles were assessed together.Forty-two subjects completed the study. The mean EPO concentration-time profiles were comparable between the two formulations. The geometric mean ratios (90% CI) of the Cmax and AUCinf were 0.908 (0.843-0.978) and 1.049 (0.999-1.101), respectively, both of which were within the regulatory range of 0.80-1.25. Additionally, the PD and tolerability profiles were similar between the two formulations. The time-matched serum EPO concentration and PD markers presented a counterclockwise hysteresis, suggesting a time delay between the measured concentration and the response. Both formulations were well tolerated, and production of anti-drug antibodies was not observed.The two epoetin alfa formulations had similar PK, PD and tolerability profiles. Furthermore, both formulations had a similar time-matched serum EPO concentration and erythropoietic response profile. Thus, the two formulations are expected to be used interchangeably in clinical settings.

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A Relative Bioavailability Study of Two Misoprostol Formulations Following a Single Oral or Sublingual Administration.

Publications

A Relative Bioavailability Study of Two Misoprostol Formulations Following a Single Oral or Sublingual Administration.

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