The effect of omeprazole on the pharmacokinetics of metronidazole and hydroxymetronidazole in human plasma, saliva and gastric juice

Jessa, M.J., Goddard, A.F., Barrett, D.A., Shaw, P.N. and Spiller, R.C. (1997) The effect of omeprazole on the pharmacokinetics of metronidazole and hydroxymetronidazole in human plasma, saliva and gastric juice. British Journal of Clinical Pharmacology, 44 3: 245-253. doi:10.1046/j.1365-2125.1997.t01-1-00572.x


Author Jessa, M.J.
Goddard, A.F.
Barrett, D.A.
Shaw, P.N.
Spiller, R.C.
Title The effect of omeprazole on the pharmacokinetics of metronidazole and hydroxymetronidazole in human plasma, saliva and gastric juice
Journal name British Journal of Clinical Pharmacology   Check publisher's open access policy
ISSN 0306-5251
1365-2125
Publication date 1997-09-01
Year available 1997
Sub-type Article (original research)
DOI 10.1046/j.1365-2125.1997.t01-1-00572.x
Volume 44
Issue 3
Start page 245
End page 253
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Aims
To evaluate the effect of omeprazole on the pharmacokinetics of metronidazole and hydroxymetronidazole in plasma, gastric juice and saliva following intravenous infusion or oral dosing of metronidazole.

Methods
Eight volunteers received single doses of metronidazole (400 mg) intravenously and orally, whilst taking placebo or omeprazole (40 mg, twice daily for 5 days) in a randomized 4-way crossover study. Metronidazole and hydroxymetronidazole concentrations in plasma, saliva and gastric juice samples were determined by h.p.l.c. Pharmacokinetic parameters for metronidazole and hydroxymetronidazole were calculated, and the significance of the mean differences in parameters between omeprazole and placebo co-administration was assessed using a two-tailed, paired t-test.

Results
There were no significant differences (P<0.05) in any of the plasma or saliva pharmacokinetic parameter values for metronidazole between volunteers receiving omeprazole or placebo when metronidazole was administered either as an intravenous infusion or orally. Following intravenous administration of metronidazole to the placebo group and omeprazole treated group respectively, the gastric transfer of metronidazole was significantly reduced from 15.5±10.4% to 2.6±1.0% of the dose (P=0.007; 95% CI of difference 4.8 to 21.0) with concomitant changes in the metronidazole AUC (from 77.5±18.0 &mu;mol l−1 h to 352.6±182.1 &mu;mol l−1 h; P=0.0003; 95% CI of difference 127.6 to 422.7), Cmax (from 61.4±26.5 &mu;mol l−1 to 271.8±104.3 &mu;mol l−1; P=0.0001; 95% CI of difference 118.6 to 302.1). Similarly, the gastric juice AUC of hydroxymetronidazole was significantly reduced from 3.2±1.9 &mu;mol l−1 h to 1.5±0.8 &mu;mol l−1 h of the dose (P=0.0043; 95% CI of difference 0.4 to 3.0) with a concomitant change in Cmax (from 5.0±2.5 &mu;mol l−1 to 3.0±1.2 &mu;mol l−1; P=0.0007; 95% CI of difference 0.7 to 3.4).

Conclusions
Omeprazole had little effect on the plasma and salivary pharmacokinetics of metronidazole (or its hydroxymetabolite) after intravenous or oral administration, but it did have a substantial effect on the pharmacokinetics of metronidazole and hydroxymetronidazole in gastric juice.
Keyword Metronidazole
Hydroxymetronidazole
Omeprazole
Human Volunteer Study
Pharmacokinetics
Plasma
Gastric Juice
Saliva
Gastric Transfer
Helicobacter Pylori
Helicobacter-pylori Infection
Triple Therapy
Metabolite
Efficacy
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article first published online: 2 October 2003.

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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