geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Proton pump inhibitor co-medication reduces mycophenolate acid drug exposure in heart transplant recipients


, : Proton pump inhibitor co-medication reduces mycophenolate acid drug exposure in heart transplant recipients. Journal of Heart and Lung Transplantation 28(6): 605-611

Proton pump inhibitors (PPIs) are often prescribed for gastrointestinal discomfort after heart transplantation (HTx). This study investigates the impact of PPI use on mycophenolate acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) and tacrolimus (Tac). MPA post-dose plasma concentrations at 0 to 2 hours were obtained by high-performance liquid chromatography (HPLC) in 21 patients on pantoprazole 40 mg/day (PPI group) and 12 patients not on pantoprazole (control group). In a subgroup, MPA plasma concentrations at 0 to 12 hours were measured to evaluate full MPA area-under-the-curve (AUC) measurements. In the PPI group, the mean daily MMF dose was 1,912 +/- 1,023 mg with mean pre-dose serum concentrations (C(0)) of 1.9 +/- 1.4 mg/liter, without a significant difference from controls. Mean post-dose MPA concentrations at 30 minutes (C(0.5h)) were significantly higher in the control group (control, 17.9 +/- 11.5 mg/liter; PPI, 6.7 +/- 4.6 mg/liter; p < 0.001). One- and 2-hour (C(1h, 2h)) MPA concentrations were persistently higher in the control group (1 hour: control, 13.8 +/- 9.1 mg/liter; PPI, 7.7 +/- 4.1 mg/liter; 2 hours: control, 7.6 +/- 4.2; PPI, 5.0 +/- 2.8 mg/liter; p < 0.05). In the subgroup with full AUC measurements, the control group had higher MPA levels 12 hours after dosing (C(12h): control, 3.3 +/- 2.4 mg/liter; PPI, 1.6 +/- 1.3 mg/liter; p < 0.05) and a significantly higher dose-adjusted AUC C(0-3h) (control, 59.5 +/- 20.7 mg/liter; PPI, 41.7 +/- 23.4 mg/liter; p < 0.05). In the subgroup, the maximum plasma concentration of mycophenolic acid (MPA C(max)) in the PPI group was significantly lower (10.1 +/- 4.7 mg/liter) than in the control group (45.5 +/- 53.5 mg/liter, p < 0.0001), whereas t(max) revealed no differences (control: 1.1 +/- 0.77 hours; PPI: 1.1 +/- 0.97 hours). Furthermore, a clear trend for more acute rejection episodes (AREs) and more transplant vasculopathy (TVP) was found in the PPI group. Patients with PPI co-medication show significantly lower MPA plasma concentrations, possibly due to decreased absorption. Therapeutic drug monitoring allows identification of patients with decreased MMF drug exposure who might be at risk for acute rejection.

US$19.90

PMID: 19481022

DOI: 10.1016/j.healun.2009.03.006


Other references

Work, Elizabeth, 1955: The action of L-amino acid oxidases on the optical isomers of a, E -diaminopimelic acid. The oxidation of the optical isomers and some amides of [alpha], [image] -diaminopimelic acid by L-amino acid oxidases from Neurospora and snake venoms was investigated. Neurospora oxidase attacked meso and L-L-diaminopimelic acid, L-diaminopimeli...

Crumrine, R.S., 1971: Postoperative hypoxia in infants and children. International Anesthesiology Clinics 9(4): 83-97

Yegorov D.G., 1995: Question of systematization of geological objects from position of information theory. Otechestvennaya Geologiya 1995(12): 70-73

Petrov, I., 1976: Histomorphologic studies on post. Zhivotnovudni nauki: 3 (4) 60-70

Gao, X-Pei.; Liu, Q.; Broman, M.; Predescu, D.; Frey, R.S.; Malik, A.B., 2005: Inactivation of CD11b in a mouse transgenic model protects against sepsis-induced lung PMN infiltration and vascular injury. To inactivate chronically the beta(2)-integrin CD11b (Mac-1), we made a transgenic model in mice in which we expressed the CD11b antagonist polypeptide neutrophil inhibitory factor (NIF). Using these mice, we determined the in vivo effects of CD11...

Henry H.L., 1985: Inhibition by ketoconazole of 25 hydroxyvitamin d 3 1 hydroxylation in chick kidney cell cultures. Federation Proceedings 44(5): 1609

Vinet, N.; Higgins, M.D., 2009: What can crystal size distributions and olivine compositions tell us about magma solidification processes in Kilauea Iki lava lake, Hawaii?. Eos, Transactions, American Geophysical Union 90.52, SUPPL

Duplais, C.; Estevez, Y., 2017: Tandem Biocatalysis Unlocks the Challenging de Novo Production of Plant Natural Products. Intimate partnership: Knowledge of the biocatalytic cascades in different cellular compartments is limited, but deciphering these systems in nature can be used to inspire synthetic strategies. Two studies report new insights into the biosynthesis...

Garcia Jesus Chavarria, 1980: Petroleum development in the Gulf of Campeche. Ocean Industry 15(11): 39-43

Murakami, T.; Nakamura, S.; Suzuki, T., 1955: A histological study on the mechanism of intestinal epithelial metaplasia in gastric mucous membrane. Gan 46(1): 9-14