Total drug clearance, pharmacokinetic

Drugs can be cleared from the body by metabolism as well as renal excretion, and when this occurs it is not possible to measure directly the amount cleared by metabolism. However, the total clearance rate (TCR), or total body clearance, of the drug can be calculated from its pharmacokinetic parameters using the following equation ... 

Ward et al. [125] investigated the disposition of 14C-radiolabeled primaquine in the isolated perfused rat liver preparation, after the administration of 0.5, 1.5, and 5 mg doses of the drug. The pharmacokinetics of primaquine in the experimental model was dependent on dose size. Increasing the dose from 0.5 to 5 mg produced a significant reduction in clearance from 11.6 to 2.9 mL/min. This decrease was accompanied by a disproportionate increase in the value of the area under the curve from 25.4 to 1128.6 pg/mL, elimination half-life from 33.2 to 413 min, and volume of distribution from 547.7 to 1489 mL. Primaquine exhibited dose dependency in its pattern of metabolism. While the carboxylic acid derivative of primaquine was not detected perfusate after the 0.5 mg dose, it was the principal perfusate metabolite after 5 mg dose. Primaquine was subject to extensive biliary excretion at all doses, the total amount of 14C-radioactivity excreted in the bile decreased from 60 to 30%i as the dose of primaquine was increased from 0.5 to 5 mg. 

The pharmacokinetic properties of the benzodiazepines in part determine their clinical use. In general, the drugs are well absorbed, widely distributed, and extensively metabolized, with many active metabolites. The rate of distribution of benzodiazepines within the body is different from that of other antiseizure drugs. Diazepam and lorazepam in particular are rapidly and extensively distributed to the tissues, with volumes of distribution between 1 L/kg and 3 L/kg. The onset of action is very rapid. Total body clearances of the parent drug and its metabolites are low, corresponding to half-lives of 20-40 hours. 

Clearance. This usually refers to the total plasm clearance (or total whole blood clearance) afte infravenous administration. In some instances the total clearance afrer an oral dose has been included if the drug is known to be well absorbed and is no subject to significant first-pass metabohsm. Numerous factors and intersubject variations ma affect the absorption, distribution, metabohsm, and excretion of drugs. These include age, sex, and disease states such as renal impairment In additior results of analyses may be subject to imavoidable analytical inaccuracies. Consequently, friere may beconsiderable variations in the observed drug concentrations and in values for pharmacokinetic... 

The effects of other antiepileptic drugs on the pharmacokinetics of lamotrigine have been studied in 62 patients with epilepsy (71). Carbamazepine, phenytoin, and phenobarbital, all enzyme inducers, increased the total oral clearance of lamotrigine, individually by 58% and in combination by nearly 200%. 

Limited pharmacokinetic data are available for this compound. Orally administered drug has a half-life of about I. hours and a total body clearance of 4.4 mL/min perkg.lh mean peak plasma concentrations are reported to van... 

Chiou, W. L., Gadalla, M. A., and Peng, G. W., Method for the rapid estimation of the total body drug clearance and adjustment of dosage regimens in patients during a constant-rate intravenous infusion, J. Pharmacokinet. Biopharm., 6(2) 135-151, 1978. 

These terms are used to compute the model-independent pharmacokinetic descriptors that follow. Total body clearance. Cl, which is the rate of drug transfer out of the body, is defined as ... 

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