Renal impairment pharmacokinetics

Czock D, Giehl M, Keller F (2000) A concept for pharmacokinetic-pharmacodynamic dosage adjustment in renal impairment the case of aminoglycosides. Clin Pharmacokinet 38(4) 367—375. Erratum in Clin Pharma-cokinet 2000 39(3) 231... 

Urinary tract Early ionic urographic agents including iodamide Uromiro Tubular secretion Difazio LT et al (1978) Pharmacokinetics of iodamide in normal subjects and in patients with renal impairment. J Clin Pharmacol 18 35-41... 

Factors reported to influence TCA plasma concentrations include disease states (e.g., renal or hepatic dysfunction), genetics, age, cigarette smoking, and concurrent drug administration. Similarly, hepatic impairment, renal impairment, and age have been reported to influence the pharmacokinetics of SSRIs. 

The pharmacokinetics of tegaserod in patients with IBS are comparable to those in healthy individuals, and similar between men and women. No dosage adjustment is required in elderly patients or those with mild-to-moderate hepatic or renal impairment [46,47]. 

Bivalirudin Pharmacokinetic Parameters and Dose Adjustments in Renal Impairment ... 

Renal function impairment The pharmacokinetics of diltiazem and verapamil in patients with impaired renal function are similar to the pharmacokinetic profile of patients with normal renal function. However, caution is still advised. Nifedipine s plasma concentration is slightly increased in patients with renal impairment. Nicardipine s mean plasma concentrations, AUC and maximum concentration were about 2-fold higher in patients with mild renal impairment. 

Renal function impairment Data in end-stage renal failure patients repeatedly treated with zolpidem did not demonstrate drug accumulation or alterations in pharmacokinetic parameters. No dosage adjustment in renally impaired patients is required however, closely monitor these patients. 

Hepatic function impairment The pharmacokinetics of oxcarbazepine and MHD have not been evaluated in severe hepatic impairment. Adjust dose in renally impaired patients. 

Renal impairment Data in pediatric patients with impaired renal function are not available however, because cefepime pharmacokinetics are similar in adult and pediatric patients, changes in dosing regimen similar to those in adults are recommended for pediatric patients. 

Mechanism of Action A third-generation cephalosporin that binds to bacterial cell membranes and inhibits cell wall synthesis. Therapeutic Effect Bactericidal, Pharmacokinetics Moderately absorbed from the GI tract. Protein binding 65%-70%, Widely distributed. Primarily excreted unchanged in urine. Minimally removed by hemodialysis, Half-life 3-4 hr (increased in renal impairment). 

Pharmacokinetics Poorly absorbed from the gastrointestinal (GI) tract. Proteinbinding 13%. Widely distributed. Partially metabolized in liver. Excreted primarily in urine. Half-life 128-149 hr (longer in renal impairment). 

Pharmacokinetics Well absorbed after PO administration. Protein binding 28%-31%. Metabolized by the liver to inactive metabolite. Eliminated primarily in urine and, to a lesser extent, in feces. Half-life 6 hr (increased in hepatic or renal impairment). 

Pharmacokinetics Rapidly and completely absorbed afterPO administration. Undergoes minimal metabolism. Excreted in urine. Half-life 1.5 hr (increased in renal impairment). 

Pharmacokinetics Poorly bound to plasma proteins unbound fraction in plasma 35%. Limited metabolism. Primarily eliminated in the urine (65%) and, to a lesser amount, in the feces. Removed by hemodialysis. Half-life 2 hr. Clearance is significantly decreased in severe renal impairment (creatinine clearance less than 30 ml/min). 

Pharmacokinetics Well absorbed from the G1 tract. Protein binding 25%-30%. Metabolized in the liver to active metabolite. Primarily excreted in urine. Not removed by hemodialysis. Half-life 3-7 hr metabolite, 9-13 hr (increased in hepatic or renal impairment. 

It is excreted in breast milk at concentration constantly higher than those in maternal plasma. The elimination of pseudoephedrine is reduced in renal impairment. Hepatic dysfunction is unlikely to affect the pharmacokinetics of the drug. 

Pharmacokinetics According to the product label, the pharmacokinetics of eptihbatide are linear and dose proportional. Plasma elimination half-life is approximately 2.5 hours. The extent of eptihbatide binding to human plasma protein is about 25% its mean volume of distribution is 185mPkg. Clearance in patients with coronary artery disease is 55-58 ml/kg per hour. Clinical studies have included 2418 patients with serum creatinine between 1.0 and 2.0mg/dl without dose adjustment. No data are available in patients with more severe degrees of renal impairment, but plasma eptihbatide levels are expected to be higher in such patients. Patients in clinical studies were older than the subjects in clinical pharmacology studies, and they had lower total body eptihbatide clearance and higher eptihbatide plasma levels. Men and women showed no important differences in the pharmacokinetics of eptihbatide. 

The pharmacokinetics of a single oral dose of exemestane 25 mg have been studied in postmenopausal subjects with normal hepatic function (n = 9), moderately impaired hepatic function (n = 9), severely impaired hepatic function (n = 8), normal renal function (n = 6), moderately impaired renal function (n = 6), and severely impaired renal function (n = 7) (36). Exposure to exemestane was increased two- to three-fold in patients with hepatic impairment the apparent oral clearance and apparent volume of distribution of exemestane were reduced. Renal impairment was also associated with two- to three-fold increases in exposure due to reduced clearance. However, because exemestane has a relatively large safety margin, the authors considered that these effects were of no clinical significance. 

Jannuzzo MG, Poggesi I, Spinelli R, Rocchetti M, Cicioni P, Buchan P. The effects of degree of hepatic or renal impairment on the pharmacokinetics of exemestane in postmenopausal women. Cancer Chemother Pharmacol 2004 53(6) 475-81. 

Schumacher S, Abbasi I, Weise D, Hatorp V, Sattler K, Sieber J, Hasslacher C. Single- and multiple-dose pharmacokinetics of repaglinide in patients with type 2 diabetes and renal impairment. Eur J Clin Pharmacol 2001 57(2) 147-52. 

Profozic V, Mrzljac V, Nazar I, Metelko Z, Rosenkranz B, Lange C, Malerczyk V. Safety, efficacy, and pharmacokinetics of glimepiride in diabetic patients with renal impairment over a 3-month period. Diabetol Croat 1999 28 25-32. 

Up to the present time no studies have been published on the pharmacokinetics of eszopiclone in elderly patients or patients with hepatic or renal impairment. 

I Eriksson UG, Johansson S, Attman PO, et al. Influence of severe renal impairment on the pharmacokinetics and pharmacodynamics of oral ximelagatran and subcutaneous melagatran. Clin Pharmacoki net 2003 42 743-753. 

The pharmacokinetics of pantoprazole do not appear to be modified to any clinically relevant extent by renal impairment. Hemodialysis does not appear to significantly influence the pharmacokinetics of Pantoprazole or its main dealkylated conjugate in patients with renal disease or end stage renal failure [1, 21]. 

Ashley, C., 2006, Clinical pharmacokinetics in renal impairment. In Dhillon, S. and Kostrzewski, A. (Eds), Clinical pharmacokinetics, Pharmaceutical Press, 53-77. 

The pharmacokinetics of modafinil are not affected, to a clinically significant extent, by volunteer age or food intake, but both the maximum plasma concentration and the elimination half-life of the drug are increased in patients with hepatic or renal impairment. It was found that peak plasma concentrations of modafinil were reached 2.3 h after a single 200 mg oral dose in healthy volunteers. Over the dose range 200 to 600 mg, the pharmacokinetics of modafinil were linear and dose dependent. Orally administered modafinil is extensively biotransformed in the liver to the inactive metabolites modafinil acid 6 (major metabolite) and modafinil sulphone 7 (minor metabolite), before being eliminated primarily in the... 

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