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1.
Clin Pharmacol Ther ; 81(2): 228-34, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17192769

ABSTRACT

It is currently not clear whether the concentration-time curves of the immunosuppressants differ with respect to the CYP3A5, MDR1, or MRP2 genotype in dose-adapted stable kidney transplant patients. Dose/trough concentration ratios were obtained in 134 tacrolimus and 20 sirolimus-treated patients, and plasma concentration-time profiles were obtained from 16 (tacrolimus) and 10 (sirolimus) patients. Genotyping was carried out for CYP3A5 6986A>G; ABCB1 2677G>T/A, 3435C>T and ABCC2 -24C>T; 1249G>A; 3972C>T. Dose/trough concentration ratios were 0.67+/-0.3 and 1.36+/-0.73 x 10(3) l (P<0.00001) for tacrolimus and 0.42+/-0.17 and 0.84+/-0.46 x 10(3) l (P=0.18) for sirolimus in CYP3A5 non-expressors and expressors. The unadjusted tacrolimus area under curve (AUC)(0-12) was 106.8+/-17.5 ng/ml x h compared with 133.3+/-42.2 ng/ml x h (P=0.37) without affecting serum creatinine. Mean unadjusted AUC(0-24) of sirolimus did not differ significantly either. Therefore, CYP3A5 expressor status and not transporter variants is a main determinant of oral clearance, particularly for tacrolimus. Dose adaptation according to trough levels, however, appears to be sufficient to maintain similar concentration-time profiles.


Subject(s)
Cytochrome P-450 Enzyme System/genetics , Kidney Transplantation , Sirolimus/pharmacokinetics , Tacrolimus/pharmacokinetics , Adult , Aged , Area Under Curve , Biological Availability , Calcium Channel Blockers/metabolism , Calcium Channel Blockers/pharmacokinetics , Calcium Channel Blockers/therapeutic use , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System/metabolism , Drug Therapy, Combination , Female , Genetic Variation , Genotype , Half-Life , Humans , Immunosuppressive Agents/metabolism , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Multidrug Resistance-Associated Protein 2 , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/metabolism , Mycophenolic Acid/pharmacokinetics , Mycophenolic Acid/therapeutic use , Prednisolone/metabolism , Prednisolone/pharmacokinetics , Prednisolone/therapeutic use , Sirolimus/metabolism , Sirolimus/therapeutic use , Tacrolimus/metabolism , Tacrolimus/therapeutic use
3.
Klin Med (Mosk) ; 80(9): 4-9, 2002.
Article in Russian | MEDLINE | ID: mdl-12416216

ABSTRACT

The analysis of the literature data on quality of life (QL) in arterial hypertension (AH) demonstrates that ACE inhibitors and calcium antagonists improve QL while such data on diuretics effect are contradictable. The comparison of pharmacological and surgical treatment effects on QL in patients with coronary heart disease shows that functionally and emotionally CHD patients benefit more from coronary artery bypass surgery. In early chronic cardiac failure QL falls because of the necessity to take treatment, lower everyday activity, work limitations. Later, QL deterioration depends on severity of cardiac activity decompensation is independent of central hemodynamics, myocardial contractility and psychological status of the patient. Adequate use of QL assessment may raise efficacy of treatment of circulatory diseases.


Subject(s)
Cardiovascular Diseases , Quality of Life , Activities of Daily Living , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Calcium Channel Blockers/therapeutic use , Cardiovascular Diseases/therapy , Chronic Disease , Coronary Artery Bypass , Coronary Disease/drug therapy , Coronary Disease/psychology , Coronary Disease/surgery , Diuretics/therapeutic use , Emotions , Heart Failure/drug therapy , Humans , Hypertension/drug therapy
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