Dose Adjustment in Renal Disease

GENERAL APPROACHES FOR DOSE ADJUSTMENT IN nephritic DISEASE Renal insufficiency can markedly alter one or more of the pharmacokinetic parameters of a window pane including oral bioavailability, volume of distribution, drug binding to plasma proteins, and most importantly the rates of transfiguration and excretion, i. e. , drug clearance.. To minimize drug toxicity and maximize healing(predicate) benefits, it is a good deal necessary to adjust drug sexually transmitted disease in proportion to the degree of nephritic insufficiency. A drug will most belike require dose allowance in renal disease if 1.A substantial fraction ( 40%) of the drug dose is excreted by the kidney either unchanged or as an active (or toxic) metabolites. 2. The drug or its active metabolite has a narrow therapeutic window such that drug accumulation cannot be tolerated. 3. The kidney is a major site for the inactivation of the drug. This applies mainly to peptides like insulin, glucagon, PTH, and imipe nem. 4. There is a significant drop in the binding of the drug to plasma proteins. For instance, a decrease in the protein binding from 99 to 95% results in a fourfold rise in the unbound, active drug concentration.Dose adjustment may use up one or a combination of the following measures 1. Extension of the dosing musical interval. 2. Reduction of the maintenance dose. 3. Administration of a loading dose. 4. Monitoring blood serum drug levels. FACTORS IN CHOOSING OF DOSE ADJUSTMENT APPROACH Factors to consider when choosing give up dose adjustment approach are the class of drug ,the amplitude of the peak-trough fluctuation relative to the therapeutic index, magnitude of the dose with respect to the dose strength to be marketed and practicality of calculated dosing interval.Pharmacokinetic simulations can be especially helpful in visualizing the impact of various dose and interval changes and interval changes on the concentration time (C-T) profile at steady put up. Reduced elim ination of a drug prolongs its half life (t? ) as well as the time required for the serum level to reach a steady carry (4 times t? ). Therefore, whenever it is clinically desirable to rapidly achieve a therapeutic steady state level a loading dose should administered.To maintain a therapeutic level and, at the said(prenominal) time, avoid drug accumulation and toxicity in a patient with reduced renal function, the clinician mustiness consider reducing the size of the maintenance dose or the dosing frequency or both. In general, this step-down should in like manner be proportional to the degree of renal impairment , but should also take into depict adaptive or compensatory changes in the metabolism and excretion of the drug through non-renal routes. MAINTENANCE DOSE drop-off METHOD The maintenance dose reduction mode is employ whenever a more constant (less oscillating) serum drug level is therapeutically preferable (e. . , ? -lactam antibiotics) Let us assume that one has already specify a safe and effective dose regime for use in frequent patients. This normal dose regimen is then adjusted according to dose fraction by two basic procedures. starting method termed as constant interval, dose-reduction (DR) reduces the dose (D) by a factor of the dose fraction. Dose interval is the same as that used in the health person. D renal failure = D normal Kf t renal failure = t normal INTERVAL EXTENSION METHODThe second method referred to as constant dose, interval-extension(IE) extends dose interval by inverse of dose fraction, a value referred to as the dose interval multiplier t renal failure = t normal (1/ kf) D renal failure = D normal This type of dose adjustment strategy may also be implemented through the use of a nomogram where the dosage interval multiplier for this IE regimen is simply read off a plot of creatinine clearance Interval extension method is used for drugs for which a constant serum level is either unnecessary (eg, vigabatrin) or undesirable (e. g. , aminoglycoside antibiotics). This method is also used for drugs that normally have long elimination t?. However, a combination of the two methods is often used. In addition, for a drug whose therapeutic serum level range is known and routinely measured, dosage adjustment is often guided by monitoring the serum drug level and the patients response in terms of the therapeutic benefit and adverse drug reactions (toxicity). Reference http//www. hedrugmonitor. com/RIT97. html http//books. google. com. pk/books? id=qXw33GaQF9IC=PA288=PA288=general+approaches+to+dose+adjustment+in+renal+patients=bl=IKsqNAp2nU=jglKfgGimUFQ_xBN9cGKPPRsC2E=en=CxbTStLaAo-QkQX1_N30Aw=X=book_result=result=7=0CCMQ6AEwBjgKv=onepage=general%20approaches%20to%20dose%20adjustment%20in%20renal%20patients= ill-advised http//www. gbv. de/du/ work/toc/bs/380847361 http//books. google. com. pk/books? id=9324ILATCgMC=PA288=general+approaches+to+dose+adjustment+in+renal+DISEASEv=onepage=general%20approa ches%20to%20dose%20adjustment%20in%20renal%20DISEASE=false