Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to explore the effects of common genetic polymorphisms of cytochrome P450 (CYP)3A4, CYP3A5, cytochrome P450 oxidoreductase (POR) and multidrug resistance protein 1 (MDR1) on the pharmacokinetics and pharmacodynamics of amlodipine in primary hypertensive patients. The mild-to-moderate essential hypertension patients were recruited to complete the genotyping of CYP3A4, CYP3A5, POR and MDR1 by sequencing. After a 1-week placebo washout period, the subjects received 5 mg oral amlodipine daily for 4 weeks. Serial blood samples were collected prior to the last dosing, and 2, 6 and 24 h post-dosing. Blood pressures were measured prior and subsequent to dosing, and the demographical data were also collected. The blood samples were collected for laboratory testing. The plasma concentrations of amlodipine were determined by high-performance liquid chromatography/tandem mass spectrometry. A total of 60 patients, including 31 males and 29 females, completed the 4-week treatment. The plasma concentration of amlodipine in females at each time point was significantly higher compared to males (P<0.05). However, no significant gender differences existed in antihypertensive efficacy. The genetic polymorphisms of MDR1 C3435T had a certain impact on the plasma concentration of amlodipine, but did not affect its antihypertensive efficacy (P>0.05). The genetic polymorphisms of CYP3A4*1G, CYP3A5*3 and POR A503V showed no impact on plasma concentration and efficacy of amlodipine (P>0.05). Gender and MDR1 gene polymorphism may affect the plasma concentration of amlodipine in hypertensive patients. However, there was no impact on the efficacy of amlodipine.
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PMID:Effects of genetic factors on the pharmacokinetics and pharmacodynamics of amlodipine in primary hypertensive patients. 2607 72

A 67-year-old mental institute resident was treated for smear-positive pulmonary tuberculosis. His background history included chronic essential hypertension which was well-controlled with amlodipine 10mg daily. However, his blood pressure became suboptimal one week into antitubercular treatment, necessitating escalation of antihypertensive therapy up to six medications. Following completion of antitubercular treatment, his blood pressure improved markedly. The number of antihypertensives was able to be reduced to only two after a month. We postulate that rifampicin has attenuated the therapeutic effect of amlodipine via potent induction of hepatic CYP3A4 but the failure to control the blood pressure even with medications unrelated to cytochrome P450 pathways raises the spectre of an additional interaction.
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PMID:Resistant hypertension during antituberculosis treatment: how is rifampicin implicated? 3291 34