PMID- 25920292
OWN - NLM
STAT- MEDLINE
DCOM- 20150519
LR  - 20181202
IS  - 0125-2208 (Print)
IS  - 0125-2208 (Linking)
VI  - 98
IP  - 3
DP  - 2015 Mar
TI  - Effect of proton pump inhibitor on plasma voriconazole concentration in Thai 
      patients.
PG  - 232-7
AB  - BACKGROUND: Voriconazole is an antifungal drug used for treatment of invasive 
      aspergillosis. It is metabolized mainly via the cytochrome P450 isoenzymes 
      CYP2C19, through which its enzymatic activity can be inhibited by proton pump 
      inhibitors (PPI), especially omeprazole. Previous reports demonstrated that 
      omeprazole might be used to boost plasma voriconazole levels in infected 
      patients. However; there was no difference in plasma voriconazole concentration 
      in healthy individuals, who received omeprazole versus placebo. Therefore, the 
      interaction between PPI and voriconazole may be different between healthy and 
      infected individuals. OBJECTIVE: To determine the effects of omeprazole on plasma 
      voriconazole concentration in Thai patients who had invasive fungal diseases. 
      MATERIAL AND METHOD: The present study is a prospective observational study and 
      is a sub-study of the voriconazole therapeutic drug monitoring study. Patients 
      treated with voriconazole admitted at Siriraj Hospital during July 2011 to 
      September 2013 were enrolled. Blood samples were drawn for plasma voriconazole 
      concentration assays at day 0, 3, 7, 14 and 28. Data regarding PPI use were 
      collected and analyzed in correlation with plasma voriconazole concentration. 
      RESULTS: Of 54 patients enrolled, 47 had sufficient clinical data but 46 patients 
      had complete data of voriconazole levels. Patients mean age was 47 years and 60% 
      were male. Thirty-nine patients (83%) had invasive pulmonary aspergillosis. 
      Forty-one patients (87.2%) received PPI, among which 37 (90.2%) were omeprazole. 
      Patients with PPI use had no difference in plasma voriconazole concentration, 
      when compared with those without PPI use, at day 3 (5.89 vs. 5.44 mg/L, p = 
      0.744), day 7 (5.4 vs. 5.29 mg/L, p = 0.471), day 14 (2.40 vs. 3.13 mg/L, p = 
      0.372) and day 28 (1.77 vs. 3.23 mg/L, p = 0.314). Although there was a trend 
      toward higher plasma voriconazole concentration in patients receiving higher 
      omeprazole dose (> 20 mg/day), the difference between those treated with high (> 
      20 mg/day) and low (20 mg/day) doses of omeprazole was not statistically 
      significant at day 3 (6.27 vs. 4.87 mg/L, p = 0.429), day 7 (7.44 vs. 3.78 mg/L, 
      p = 0.166), day 14 (2.52 vs. 1.68 mg/L, p = 0.534) and day 28 (2.51 vs. 1.44 
      mg/L, p = 0.154). Similarly, the duration of omeprazole use in concurrent with 
      voriconazole treatment was not associated with plasma voriconazole concentration 
      in infected patients. CONCLUSION: Omeprazole does not affect plasma voriconazole 
      concentration in infected patients. However, patients who received higher doses 
      ofomeprazole (> 20 mg/day) tend to have a higher concentrations of plasma 
      voriconazole.
FAU - Chayakulkeeree, Methee
AU  - Chayakulkeeree M
FAU - Poovipirom, Natthanan
AU  - Poovipirom N
FAU - Siengwattana, Pimkamon
AU  - Siengwattana P
FAU - Maneerattanaporn, Monthira
AU  - Maneerattanaporn M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Thailand
TA  - J Med Assoc Thai
JT  - Journal of the Medical Association of Thailand = Chotmaihet thangphaet
JID - 7507216
RN  - 0 (Antifungal Agents)
RN  - 0 (Proton Pump Inhibitors)
RN  - JFU09I87TR (Voriconazole)
RN  - KG60484QX9 (Omeprazole)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antifungal Agents/*pharmacokinetics/therapeutic use
MH  - Aspergillosis/drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Drug Monitoring/methods
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mycoses/*drug therapy
MH  - Omeprazole/administration & dosage/*pharmacology
MH  - Prospective Studies
MH  - Proton Pump Inhibitors/administration & dosage/*pharmacology
MH  - Thailand
MH  - Voriconazole/*pharmacokinetics/therapeutic use
MH  - Young Adult
EDAT- 2015/04/30 06:00
MHDA- 2015/05/20 06:00
CRDT- 2015/04/30 06:00
PHST- 2015/04/30 06:00 [entrez]
PHST- 2015/04/30 06:00 [pubmed]
PHST- 2015/05/20 06:00 [medline]
PST - ppublish
SO  - J Med Assoc Thai. 2015 Mar;98(3):232-7.