Document Detail


Serum levels and possible haemodynamic effects following anorectal application of an ointment containing nifedipine and lignocaine : a study in healthy volunteers.
MedLine Citation:
PMID:  17163278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: This study aimed to assess whether topical anorectal application of an ointment containing nifedipine (0.3% w/w) and lignocaine (lidocaine) [1.5% w/w] to healthy adult volunteers gives rise to pharmacologically relevant serum levels of the active ingredients and has any haemodynamic effects or side effects. METHODS: A dose of 3g of the ointment was circumferentially applied inside the anus to 12 healthy volunteers every 12 hours for 7 days. Blood samples were collected at 0, 30, 60, 240, 480 and 720 minutes after the first application; in addition, blood samples were collected at days 1 and 7 after multiple applications. Serum concentrations of nifedipine, its main metabolites and lignocaine were determined by a new high-performance liquid chromatography method established for the purpose of the study. Volunteers' blood pressure, heart rate, ECG status and laboratory parameters were monitored throughout the study. RESULTS: Topical application of the ointment to healthy volunteers did not produce therapeutically significant serum levels of the active ingredients and/or their active metabolites. Indeed, chromatographic signals of the active ingredients and/or nifedipine metabolites were only sporadically observed, below the quantification limits for the method, and consistent with therapeutically negligible concentrations. No serious local or systemic adverse events were observed throughout the study, and no subjects developed arrhythmias or significant ECG changes. Neither blood pressure nor mean heart rate varied significantly after application of a single dose. After multiple doses, mean systolic and diastolic blood pressure remained close to baseline levels for the duration of the study. The mean heart rate after multiple doses was about 5% below baseline level at days 1 and 7; however, these differences were not statistically significant. CONCLUSION: This study demonstrates the safety of topical anorectal application of an ointment containing nifedipine (0.3% w/w) and lignocaine (1.5% w/w) to healthy volunteers.
Authors:
Pasquale Perrotti; Lucia Grumetto; Francesco Barbato; Carmine Antropoli
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Clinical drug investigation     Volume:  26     ISSN:  1173-2563     ISO Abbreviation:  Clin Drug Investig     Publication Date:  2006  
Date Detail:
Created Date:  2006-12-13     Completed Date:  2007-02-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9504817     Medline TA:  Clin Drug Investig     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  459-67     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology, Chirurgia Gastroenterologica, A. Cardarelli Hospital, Naples, Italy.
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MeSH Terms
Descriptor/Qualifier:
Administration, Topical
Adult
Anal Canal / drug effects,  metabolism
Anesthetics, Local / administration & dosage,  blood,  pharmacokinetics
Blood Pressure / drug effects*,  physiology
Chromatography, High Pressure Liquid / methods
Electrocardiography
Female
Heart Rate / drug effects*,  physiology
Humans
Lidocaine / administration & dosage*,  blood,  pharmacokinetics
Male
Middle Aged
Nifedipine / administration & dosage*,  blood,  pharmacokinetics
Ointments
Chemical
Reg. No./Substance:
0/Anesthetics, Local; 0/Ointments; 137-58-6/Lidocaine; 21829-25-4/Nifedipine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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