ABSTRACT
The aim of this study was to determine the interaction between omeprazole and amoxicillin, being common agents used in the eradication regimen for H. pylori infection. Amoxicillin concentrations in gastric mucosa and serum were quantitatively analysed in 12 patients with non-ulcer dyspepsia following the administration of one week duration of placebo as group I and omeprazole as group II. The study was a blind, cross-over design with a one week wash out period between the two treatment groups. Six antral gastric mucosa were biopsied 90 minutes after oral administration of amoxicillin. Blood samples were collected before and after administration at intervals up to 6 hours. All samples were analysed for amoxicillin concentration using the HPLC technique. Highly intersubject variations of amoxicillin concentrations were observed. The concentration of amoxicillin in gastric mucosa ranged from 0.00-1.74 and 0.00-1.25 micrograms/mg for group I and group II, respectively, with the mean concentration of 0.25 +/- 0.48 microgram/mg for group I and 0.28 +/- 0.40 microgram/mg for group II. The difference was not statistically significant (p = 0.89). Pharmacokinetic parameters of amoxicillin in serum following regimen I and regimen II were not significantly different (p > 0.05). The mean Cmax values were 14.62 +/- 5.39 and 12.65 +/- 4.76 micrograms/ml, the Tmax were 2.3 +/- 1.0 and 2.0 +/- 0.9 hour and the AUC0-6 were 40.79 +/- 13.26 and 38.75 +/- 15.04 micrograms/ml.h in the group I and group II, respectively. From these results, we concluded that omeprazole has no effect on gastric mucosa level nor serum levels of amoxicillin. The therapeutic efficacy of using these two agents in the eradication regimen of H. pylori may be related to other factors rather than pharmacokinetic interaction.
Subject(s)
Dyspepsia/drug therapy , Gastric Mucosa/drug effects , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Omeprazole/administration & dosage , Adult , Amoxicillin/administration & dosage , Amoxicillin/blood , Drug Interactions , Dyspepsia/microbiology , Enzyme Inhibitors/administration & dosage , Female , Humans , Male , Middle Aged , Penicillins/administration & dosage , Penicillins/blood , Probability , Reference ValuesABSTRACT
A rapid, sensitive and specific high-performance liquid chromatographic assay for the quantification of nifedipine in human plasma was developed, satisfactorily validated and applied to samples of plasma from healthy volunteers. The sample pre-treatment incorporating protein denaturation by urea and ethyl acetate extraction compared favourably in terms of selectivity with previously published methods. The limit of quantitation of this reversed-phase LC method was 7.0 ng ml-1 for the analysis of 0.5 ml samples.
Subject(s)
Chromatography, High Pressure Liquid , Nifedipine/blood , Acetates/chemistry , Administration, Oral , Calibration , Drug Stability , Half-Life , Humans , Nifedipine/administration & dosage , Nifedipine/pharmacokinetics , Reference Standards , Urea/chemistryABSTRACT
The pharmacokinetics and disposition of etretinate (ET) and its metabolites, etretin (ETA) and isoetretin (c-ETA), were studied in the dog. Administration of ET, ETA, and c-ETA by several routes of administration allowed the use of a physiologically based model to assess the relative contributions of absorption and presystemic metabolism to the oral bioavailability of these compounds. The large Vdss (214 +/- 228 liters/kg) of ET and terminal half-life of greater than 300 hr indicated the wide distribution and prolonged storage of ET in the tissues. After a dose of ET, its two metabolites, ETA and c-ETA, were also detectable in the plasma. The oral bioavailability of ET in the dog was 52.5% with 95.4% of the dose available for absorption from the gut lumen. Of the ET that was absorbed from the gut lumen, 26.4% and 25.5% was removed by the gut wall and liver, respectively. ETA was found to be a formation rate-limited metabolite of ET. Although the oral bioavailability of ETA could not be determined because its administration was not possible by the iv route, it appeared that only 16% of an orally administered dose entered the portal circulation from the gut. c-ETA was detected after administration of either ET or ETA. ETA and c-ETA were shown to be interconvertible metabolites, but the equilibrium of the conversion between c-ETA and ETA favored the formation of ETA. The oral bioavailability of c-ETA was 42.4%, but the liver showed little metabolic activity toward c-ETA.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Etretinate/pharmacokinetics , Intestinal Mucosa/metabolism , Acitretin , Animals , Biological Availability , Catheterization , Dogs , Dose-Response Relationship, Drug , Etretinate/administration & dosage , Etretinate/blood , Injections, Intravenous , Intestinal Absorption , Intestines/drug effects , Male , Models, Biological , Tretinoin/administration & dosage , Tretinoin/analogs & derivatives , Tretinoin/blood , Tretinoin/pharmacokineticsABSTRACT
The oral biovailability of etretinate (ET) and its presystemic loss due to pulmonary extraction were studied in the rat. The oral biovailability was found to be 15%. The percentage of a dose of ET escaping pulmonary extraction was estimated to be 49%. These data suggest substantial presystemic loss of ET, including significant extraction by the lungs.
