1993
DOI: 10.1128/aac.37.5.1056
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Pyrimethamine inhibits renal secretion of creatinine

Abstract: The mechanism of increased serum creatinine after administration of pyrimethamine and dapsone was evaluated for six healthy volunteers. Serum parameters, urine sediment, and clearances of creatinine, inulin, and para-aminohippurate were assessed prior to and 28 h after the ingestion of a single, combined dose of 100 mg of pyrimethamine and 200 mg of dapsone. In a second series, the same renal function tests were performed for nine human immunodeficiency virus-infected men before and after 1 month of prophylact… Show more

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Cited by 57 publications
(38 citation statements)
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“…Mild to moderate and reversible elevation of SCr and decrease in creatinine renal clearance (CL cr ) has been reported, which can be attributed to inhibition of creatinine transporters without affecting renal function per se (Arya et al, 2013(Arya et al, , 2014. This is supported by the clinical observation that several drugs, such as cobicistat (Lepist et al, 2014), pyrimethamine (Opravil et al, 1993), cimetidine (Dubb et al, 1978), and trimethoprim (Berglund et al, 1975), lead to increased levels of SCr without affecting kidney function. Such observations have also been reported for several recently approved drugs, including crizotinib Camidge et al, 2014) and dolutegravir (Koteff et al, 2013).…”
Section: Introductionsupporting
confidence: 49%
“…Mild to moderate and reversible elevation of SCr and decrease in creatinine renal clearance (CL cr ) has been reported, which can be attributed to inhibition of creatinine transporters without affecting renal function per se (Arya et al, 2013(Arya et al, , 2014. This is supported by the clinical observation that several drugs, such as cobicistat (Lepist et al, 2014), pyrimethamine (Opravil et al, 1993), cimetidine (Dubb et al, 1978), and trimethoprim (Berglund et al, 1975), lead to increased levels of SCr without affecting kidney function. Such observations have also been reported for several recently approved drugs, including crizotinib Camidge et al, 2014) and dolutegravir (Koteff et al, 2013).…”
Section: Introductionsupporting
confidence: 49%
“…Alone and in combination with dapsone, this drug was reported to increase plasma creatinine by 6 20% in healthy volunteers and by 27% in HIVinfected patients [38]. In this study, creatinine clearance decreased by 27%, whilst inulin clearance remained unchanged.…”
Section: Pyrimethaminesupporting
confidence: 43%
“…The increases in SC are explained most readily by the clinically benign phenomenon of the inhibition of the tubular secretion of creatinine, which manifests in the present study's data as a decrease in EGCE, a parameter that represents CrCL not attributable to glomerular filtration. The inhibition of tubular secretion has been described as an effect of several marketed drugs, including pyrimethamine, cimetidine, and trimethoprim (1,5,7,8,12,14).…”
Section: Discussionmentioning
confidence: 99%
“…Plasma samples for PK analysis were collected before dosing each day during the treatment period (i.e., days 1 through 8) on the following schedule: 1, 2, 3, 4, 5,6,7,8,12, and 16 h after dosing on days 1 and 8; 24, 30, and 36 h after the day 8 dosing (i.e., during day 9); approximately 48, 72, and 96 h after the day 8 dosing (i.e., on days 10, 11, and 12); and during the follow-up visit on day 15 or on early withdrawal from the study. Additionally, for subjects in all cohorts except cohort 1, blood samples for PK were drawn on day 5 at 1, 2, 3, 4, 5,6,7,8,12, and 16 h after dosing. Blood and urine samples also were collected for measurement of iohexol, PAH, and CrCL before dosing and on days 5, 8, and 15 (Table 1).…”
Section: Methodsmentioning
confidence: 99%
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