Renal disease pharmacokinetics

Dettli L (1976) Drag dosage in renal disease. Clin Pharmacokinet 1(2) 126—1115. 

Many laboratory animal models have been used to describe the toxicity and pharmacology of chloroform. By far, the most commonly used laboratory animal species are the rat and mouse models. Generally, the pharmacokinetic and toxicokinetic data gathered from rats and mice compare favorably with the limited information available from human studies. PBPK models have been developed using pharmacokinetic and toxicokinetic data for use in risk assessment work for the human. The models are discussed in depth in Section 2.3.5. As mentioned previously, male mice have a sex-related tendency to develop severe renal disease when exposed to chloroform, particularly by the inhalation and oral exposure routes. This effect appears to be species-related as well, since experiments in rabbits and guinea pigs found no sex-related differences in renal toxicity. 

Pharmacokinetics Poorly absorbed from the G1 tract. Protein binding greater than 98%. Metabolized in the liver. Minimally eliminated in urine. Plasma levels are markedly increased in chronic alcoholic hepatic disease, but are unaffected by renal disease. Half-life 14 hr. 

Figure 7.6 Structure of remifentanil and its major metabolite formed by ester hydrolysis. contrast, alfentanil has an intermediate hepatic extraction (0.3-0.5) and alfentanil clearance will be sensitive to changes in both liver blood flow and reduced enzyme capacity in patients with liver disease. Although the kidneys play a minor role in the elimination of most opioids, renal disease can influence their pharmacokinetic profile, secondary to alterations in plasma proteins and intra- and extravascular volumes. Neither the pharmacokinetics nor the pharmacodynamics of remifentanil is significantly altered in patients with liver or renal disease.

Thompson-Culkin K, Zussman B, Miller AK, Freed MI. Pharmacokinetics of rosiglitazone in patients with end-stage renal disease J Int Med Res 2002 30(4) 391-9. 

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]. 

Pharmacokinetics Slow intravenous infusion is employed for treatment of systemic infections or for prophylaxis. Because vancomycin is not absorbed after oral administration, this route is only employed for the treatment of antibiotic-induced colitis due to Q difficile. Inflammation allows penetration into the meninges. Metabolism is minimal 90-100 % is excreted by glomerular filtration. [Note Dosage must be adjusted in renal failure since the drug will accumulate. Normal half-life is 6-10 hours compared to over 200 hours in end-stage renal disease.]... 

Reidenberg MM, Drayer DE. Alteration of drug-protein binding in renal disease. Clin Pharmacokinet 1984 9(suppl l) 18-26. 

Diseases such as hepatic or renal diseases can influence the incidence of ADRs by altering the pharmacokinetics of drugs, such as absorption, distribution, metabolism, or excretion. 

The renal clearance of the drug is proportional to endogenous creatinine clearance, irrespective of the mechanisms (i.e., filtration, reabsorption, or secretion), and the creatinine clearance is used as an indicator of the severity of the disease. Furthermore, it is possible to predict the half-life of a drug in a patient with renal disease based on the creatinine clearance and on a knowledge of the pharmacokinetics of the drug in normal subjects, as illustrated with cefazolin in Fig. 3. 

Adjepon-Yamoah KK, Edwards G, Breckenridge AM, Orme ML, Ward SA. The effect of renal disease on the pharmacokinetics of diethylcarbamazine in man. Br J Clin Pharmacol 1982 13(6) 829-34. 

Aweeka FT, Jacobson MA, Martin-Munley S, Hedman A, Schoenfeld P, Omachi R, Tsunoda S, Gambertogho JG. Effect of renal disease and hemodialysis on foscamet pharmacokinetics and dosing recommendations. J Acquir Immune Defic Syndr Hum Retrovirol 1999 20(4) 350-7. 

Pharmacokinetics and safety of iomeprol in healthy volunteers and in patients with renal impairment or end-stage renal disease requiring hemodialysis. Invest Radiol 2001 36(6) 309-16. 

Sica DA, Gehr TW. The pharmacokinetics of angiotensin-converting enzyme inhibitors in end-stage renal disease. Semin Dialysis 1994 7 205-213. 

The absolute bioavailability of only a few drug compounds is affected by ESKD. An increase in bioavailability as the result of a decrease in metabolism during the drug s firstpass through the gastrointestinal tract and liver has been noted for some /3-blockers (i.e., bufu-ralol, oxprenolol, propranolol, and tolamolol), dextropropoxyphene, and dihydrocodeine. Although the bioavailability of these compounds is increased, clinical consequences (development of excessive or unexpected adverse effects) have only been demonstrated with dextropropoxyphene and dihydrocodeine. The lack of association between the pharmacokinetic profile and clinical consequences of the /3-blockers may result from an alteration in the responsiveness of patients with renal disease to these agents, as has been reported with propranolol in the elderly. ... 

---