Pharmacokinetic and bioavailability variations in renal disease

Abstract

The mammal’s kidney demonstrates a high degree of complexity both structurally and functionally and as a consequence plays a vital role in homeostatic functions which include reuptake, secretion, metabolism and endocrine. Chronic kidney diseases, an example of uremia, has an effect on both morphology and physiology of the kidney which may alter the pharmacokinetics of the drugs. Uremia can affect drug pharmacokinetics by modifying drug elimination directly. Bioavailability of the drug during severe uremia is diminished. Observed volume of distribution (Vd) is dependent on protein binding characteristics in plasma, body tissues and water. In a state of disease due to reduction of drug and protein complexes, Vd increases. Also half-life increases due a reduced glomerular filtration rate (GFR). Renal abnormalities cause reduction in binding of plasma proteins with numerous drugs and as consequence metabolic clearance of such drug molecules will increase. So we can conclude that dosing adjustments are necessary for patients with abnormal renal functioning. These adjustments can include reduction in recommended dosage levels and/or increase of subsequent dosage intervals to reach therapeutic goals of safety and efficacy. During drug development, studies must be carried out to assess the effect of impaired renal function on the drug. Such studies are not required for monoclonal antibodies, gaseous and volatile drugs which are eliminated via the lungs. For drugs to be used by end stage renal diseases (ESRD), treated by dialysis, pharmacokinetics must be studied and the related conditions with and without dialysis should be studied in order to discover which magnitude dialysis is responsible for the purging of both the drug or its dynamic metabolites which may be potentially active. Appropriate dosage adjustments are based on creatinine levels alone. An extensive evaluation on pharmacokinetics of various drugs in patients with renal diseases suggests the dosage adjustments are necessary to achieve the targeted therapeutic outcome and prevent drug serum levels crossing the toxic threshold. The purpose of review is to investigate the pharmacokinetic and bioavailability variations and its effect on patients with renal impairments.