Phenobarbital clearance

Drugs affecting fiver enzymes may alter phenobarbital metabolism, but phenobarbital clearance is not affected by fiver blood flow. The elimination of phenobarbital is linear. Because tubular reabsorption of phenobarbital is pH dependent, the amount excreted renally can be increased by giving diuretics and urinary alkalinizers." ... 

Carbamazepine serum levels are reduced to some extent by phenobarbital, and carbamazepine-10,11-epoxide levels are raised. In children, phenobarbital clearance is decreased by carbamazepine. 

Factors that may enhance theophylline clearance and result in the need for higher doses include tobacco and marijuana smoking, hyperthyroidism, and use of drugs such as phenytoin, phenobarbital, and rifampin. 

In addition, treatment of animals with phenobarbital not only increased overall rates of metabolism and clearance, but also shifted the metabolite patterns. One of the more common methods used for determining an exposure to (or the amount of a metabolite produced) is to determine an area under the curve (AUC) for the metabolite. Further, one of the more common methods for representing a racemically preferred metabolite is to calculate the ratio of the R to the S. For example, the 3-decholoro metabolite of ifosfamide was produced in higher amounts from the R enantiomer while the 2-decholorometabolite was the major metabolite produced from the R enantiomer in naive animals. Treatment with phenobarbital shifted the metabolism so that the 3-dechloro metabolite was no longer the major metabolite for the S enantiomer. 

CYP 450 Drugs that induce liver enzymes (eg, phenytoin, carbamazepine, phenobarbital) increase the metabolism and clearance of zonisamide and decrease its half-life. Concurrent medication with drugs that induce or inhibit CYP3A4 would be expected to alter serum concentrations of zonisamide. Zonisamide is not expected to interfere with the metabolism of other drugs that are metabolized by cytochrome P450 isozymes. 

The apparent clearance of lamotrigine is affected by the coadministration of AEDs. Lamotrigine is eliminated more rapidly in patients who have been taking hepatic enzyme inducing antiepileptic drugs (ElAEDs), including carbamazepine, phenytoin, phenobarbital, and primidone. 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

Valproate metabolism may be induced by other anticonvulsants, including carbamazepine, phenytoin, primidone, and phenobarbital, resulting in an increased total clearance of valproate and perhaps decreased efficacy. 

Cyclosporin is metabolised by the hepatic cytochrome P-450 enzyme system, and enzyme induction by phenobarbital, phenytoin, carbamazepine, or rifampicin will drastically increase the clearance of cyclosporin. Concurrent administration of these drugs has caused rejection of transplanted organs. Conversely, the use of enzyme inhibitors, such as erythromycin or the azole antifungal agents, e.g. ketoconazole, will increase the blood concentrations of cyclosporin leading to an increased risk of toxic side effects. 

Primidone has a larger clearance than most other antiseizure drugs (2 L/kg/d), corresponding to a half-life of 6-8 hours. clearance is approximately half that of primidone, but phenobarbital has a very low clearance. The appearance of phenobarbital corresponds to the disappearance of primidone. Phenobarbital therefore accumulates very slowly but eventually reaches therapeutic concentrations in most patients when therapeutic doses of primidone are administered. During chronic therapy, phenobarbital levels derived from primidone are usually two to three times higher than primidone levels. 

Metronidazole has been reported to potentiate the anticoagulant effect of coumarin-type anticoagulants. Phenytoin and phenobarbital may accelerate elimination of the drug, whereas cimetidine may decrease plasma clearance. Lithium toxicity may occur when the drug is used with metronidazole. 

Efavirenz inhibits the plasma levels of indinavir, saquinavir and amprenavir and increases the concentrations of ritonavir and nelfinavir. It also lowers the plasma levels of methadone, phenytoin, carbamazepine and phenobarbital. Drugs that stimulate the cytochrome P-450 system will increase its clearance and should not be coadministered. 

Welch, R.M., et al. Effect of aroclor 1254, phenobarbital, and polycyclic aromatic hydrocarbons on the plasma clearance of caffeine in the rat. Clin Pharmacol Therap, 1977 22 Part 2, 791-798... 

Drugs that alter the pH of urine can significantly affect the renal excretion of other drugs. Acid urine increases the effectiveness of mercurial diuretics. It also accelerates the excretion of basic drugs such as meperidine, tricyclic antidepressants, amphetamines, and antihistamines. Acidic drugs, such as aspirin, streptomycin, phenobarbital, sulfonamides, nalidixic acid, and nitrofurantoin have been shown to increase renal clearance in alkaline urine (61). The possible effects of urine pH on the renal excretion of drugs has been illustrated by the observation that if urine is rendered sufficiently alkaline, the excretion of amphetamine is markedly delayed and effective blood levels, after a single dose, can be maintained for several days (62). 

Studies have been conducted on the interaction of benzene with other chemicals, both in vivo and in the environment. Benzene metabolism is complex, and various xenobiotics can induce or inhibit specific routes of detoxification and/or activation in addition to altering the rate of benzene metabolism and clearance from the body. Toluene, Aroclor 1254, phenobarbital, acetone, and ethanol are known to alter the metabolism and toxicity of benzene. 

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