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JCM vol. 3, issue 1, 2010
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COMPARATIVE BIOAVAILABILITY OF METOCLOPRAMIDE HYDROCHLORIDE AT A DOSE OF 10 MG, ADMINISTERED IN TABLET FORM ORALLY, INTRAVENOUSLY AND THROUGH A NASAL MUCOADHESIVE SPRAY
Contents:
COMPARATIVE BIOAVAILABILITY OF METOCLOPRAMIDE HYDROCHLORIDE AT A DOSE OF 10 MG, ADMINISTERED IN TABLET FORM ORALLY, INTRAVENOUSLY AND THROUGH A NASAL MUCOADHESIVE SPRAY
Original Article
Authors: Ch. Tzachev1, T. Popov2
1Medical University - Sofia, Faculty of Pharmacy, Department of Technology and Biopharmacy
2Aleksandrovska Hospital, Department of Asthma, Allergology and Clinical Immunology
Author for contacts: T.A. Popov, Clinic of Allergy & Asthma, 1, Sv. Georgi Sofiyski St., 1431 Sofia, Bulgaria, phone/fax: +359 2 9230397,e-mail: ted.popov@gmail.com
1Medical University - Sofia, Faculty of Pharmacy, Department of Technology and Biopharmacy
2Aleksandrovska Hospital, Department of Asthma, Allergology and Clinical Immunology
Author for contacts: T.A. Popov, Clinic of Allergy & Asthma, 1, Sv. Georgi Sofiyski St., 1431 Sofia, Bulgaria, phone/fax: +359 2 9230397,e-mail: ted.popov@gmail.com
Keywords: metoclopramide, mucoadhesive spray, comparative bioavailability
Abstract
Introduction: The advantage of nasal to oral form for administration of antiemetic is obvious. Its efficient administration, however, depends on the pharmacokinetic characteristics of the form. With the perspective to improve them, a mucoadhesive solution of metoclopramide hydrochloride was developed.
Objective: To compare the bioavailability of a mucoadhesive nasal spray containing metoclopramide hydrochloride to the reference oral and intravenous forms of the same drug.
Design: This was a randomized crossover clinical study comparing the plasma levels of metoclopramide in 18 healthy volunteers after taking a single dose of 10 mg nasal spray, an intravenous solution and tablets in three periods in random order. The aim was to evaluate the absolute and relative bioavailability of metoclopramide mucoadhesive nasal spray.
Materials and methods: The mucoadhesive nasal spray contained low concentration of metoclopramide hydrochloride - 5%, and an overall standard dose of 10 mg was provided by two applications of 100 μl in each nostril. The solution was isotonic, 310 mOsm/L, and is manufactured in Unipharm AD, Bulgaria. Reference tablet forms were Reglan, tablets of 10 mg produced by Schwarz Pharma. Reference injection form was Reglan, sol. injection 5 mg/ml produced by Baxter Healthcare Corp.
Results: Peak plasma levels of metoclopramide were Cmax = 44.94 (± 3.16) ng/ml, Tmax = 0.88 (± 0.08) hours for the tablet forms and Cmax = 26.99 (± 2.02) ng/ml and Tmax = 2.17 (± 0.18) hours for nasal form. 60 min. to 210 min after application, the plasma levels of metoclopramide nasal form remain without significant difference (p [t7, t8, t9, t10, t11, t12] = 0.95) but with a tendency for increase. After 60 min the concentration of metoclopramide in tablet forms sharply decreased by 15% and gradually lowered thereafter. The absolute bioavailability of the nasal spray was 59%, while of the tablets was 80.9%, the relative bioavailability of the spray was 74%
Conclusion: The mucoadhesive nasal spray provided high bioavailability when administered in low concentration (5%) and dose (10 mg). Metoclopramide hydrochloride was well-tolerated by patients and no burning, stinging or bitter taste were reported.
Introduction: The advantage of nasal to oral form for administration of antiemetic is obvious. Its efficient administration, however, depends on the pharmacokinetic characteristics of the form. With the perspective to improve them, a mucoadhesive solution of metoclopramide hydrochloride was developed.
Objective: To compare the bioavailability of a mucoadhesive nasal spray containing metoclopramide hydrochloride to the reference oral and intravenous forms of the same drug.
Design: This was a randomized crossover clinical study comparing the plasma levels of metoclopramide in 18 healthy volunteers after taking a single dose of 10 mg nasal spray, an intravenous solution and tablets in three periods in random order. The aim was to evaluate the absolute and relative bioavailability of metoclopramide mucoadhesive nasal spray.
Materials and methods: The mucoadhesive nasal spray contained low concentration of metoclopramide hydrochloride - 5%, and an overall standard dose of 10 mg was provided by two applications of 100 μl in each nostril. The solution was isotonic, 310 mOsm/L, and is manufactured in Unipharm AD, Bulgaria. Reference tablet forms were Reglan, tablets of 10 mg produced by Schwarz Pharma. Reference injection form was Reglan, sol. injection 5 mg/ml produced by Baxter Healthcare Corp.
Results: Peak plasma levels of metoclopramide were Cmax = 44.94 (± 3.16) ng/ml, Tmax = 0.88 (± 0.08) hours for the tablet forms and Cmax = 26.99 (± 2.02) ng/ml and Tmax = 2.17 (± 0.18) hours for nasal form. 60 min. to 210 min after application, the plasma levels of metoclopramide nasal form remain without significant difference (p [t7, t8, t9, t10, t11, t12] = 0.95) but with a tendency for increase. After 60 min the concentration of metoclopramide in tablet forms sharply decreased by 15% and gradually lowered thereafter. The absolute bioavailability of the nasal spray was 59%, while of the tablets was 80.9%, the relative bioavailability of the spray was 74%
Conclusion: The mucoadhesive nasal spray provided high bioavailability when administered in low concentration (5%) and dose (10 mg). Metoclopramide hydrochloride was well-tolerated by patients and no burning, stinging or bitter taste were reported.
EudraCT number: 2007-006028-36
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