Gabapentin pharmacokinetics

It is not necessary to monitor gabapentin plasma concentrations to optimize therapy. Further, because there are no significant pharmacokinetic interactions with other commonly used anti-epileptic drugs, the addition of gabapentin does not alter the plasma levels of these drugs appreciably. 

Pharmacokinetics Gabapentin bioavailability is not dose-proportional. It circulates largely unbound (less than 3%) to plasma protein and is eliminated from the systemic circulation by renal excretion as unchanged drug it is not appreciably metabolized. 

Gabapentin does not bind to plasma proteins, is not appreciably metabolized, nor induces hepatic enzyme activity (AHFS, 2000) Consequently, it does not appear to alter the pharmacokinetics of commonly used anticonvulsant drugs or oral contraceptives (Ketter et al.,... 

A more common approach in difficult to treat cases would be the combination of clomipramine with a SSRI several reports lend support to this practice (Simeon and Thatte, 1990 Figueroa et al., 1998). In this situation, careful attention to the potential pharmacokinetic interactions discussed above are recommended. Sertraline and citalopram are least likely to elevate tricyclic levels due to less potential GYP interactions. By expert consensus, second- (venlafaxine) and third-line (nefazadone and gabapentin) agents may be used when clinical response is inadequate despite a lack of controlled data. Venlafaxine may be substituted for a more typical SSRI while nefazadone or gabapentin may be added to either clomipramine or a SSRI. The combination of venlafaxine with other SSRIs is not generally recommended as it may increase the risk of a serotonin syndrome. The addition of nefazadone to SSRIs presents a lesser risk. 

Outlook Among the newer antiepileptics, gabapentin, oxycarbazepine, lamotrigine, and topiramate are now endorsed as primary monotherapeutics for both partial and generalized seizures. Their pharmacokinetic characteristics are generally more desirable than those of the older drugs. 

The combination of lithium with an anticonvulsant mood stabilizer can be beneficial. There have been reports of lithium/carbamazepine neurotoxicity, but on the other hand, lithium can benefit carbamazepine-induced leukopenia. There do not appear to be clinically important pharmacokinetic interactions of lithium with gabapentin... 

Frye MA, Kimbrell TA, Dunn RT, Piscitelli S, Grothe D, Vanderham E, Cora-Locatelli G, Post RM, Ketter TA. Gabapentin does not alter single-dose lithium pharmacokinetics. J Chn Psychopharmacol 1998 1 8(6) 461 —4. 

Blum RA, Comstock TJ, Sica DA, Schultz RW, Keller E, Reetze P, et al. Pharmacokinetics of gabapentin in subjects with various degrees of renal function. Clin Pharmacol Ther 1994 56 154-9. 

PHARMACOKINETICS Gabapentin is absorbed after oral administration and excreted unchanged, mainly in the urine. Its tj 2> when used as monotherapy, is 4-6 hours. It has no known interactions with other antiseizure drugs. 

Gabapentin does not normally affect the pharmacokinetics of car-bamazepine, phenytoin, phenobarbital or sodium valproate, and no dosage adjustments are needed on concurrent use. However, isolated reports describe increased phenytoin levels and toxicity in two patients given gabapentin. 

Gabapentin does not affect phenobarbital levels, nor is it affected by pbenobarbital. Other studies confirm that the steady-state pharmacokinetics of carbamazepme and sodium valproate are unaffected by gabapentin, and that the pharmacokinetics of gabapentin are similarly unaffected by these antiepileptics. ... 

Richens A Clinical pharmacokinetics of gabapentin. New Trends in Epilepsy Management The Role of Gabapentin International Congress and S3nnposium Series No 198, Royal Society of Me cine Services, London, NY 1993,41-6. 

Hooper WD, Kavanagh MC, Herkes GK, Eadie Ml. Lack of a pharmacokinetic interaction between phenobarbitone and gabapentin BrJ Clin Pharmacol (1991) 31,171-4. 

There is some evidence that the enzyme-inducing antiepileptics (carbamazepine, phenobarbital, phenytoin and primidone) may modestly reduce levetiracetam levels, but this is not thought to be clinically relevant. Levetiracetam does not usually alter the levels of these antiepileptics. However, some studies have found modestly raised phenytoin levels, and cases of possible carbamazepine toxicity have also been reported. There appears to be no pharmacokinetic interaction between levetiracetam and gabapentin, lamotrigine, or valproate. 

There appears to be no pharmacokinetic interaction between pregabalin and carbamazepine, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, alcohol, lorazepam, or oxycodone. However, the impairment of cognitive and gross motor function caused by oxycodone was additive with pregabalin, and pregabalin may potentiate the effects of alcohol and lorazepam. 

Gabapentin did not alter the pharmacokinetics of single-dose lithium in patients with normal renal function. 

In a double-blind study, 13 patients with normal renal function were given a single 600-mg dose of lithium either with or without gabapentin at steady state. Gabapentin did not significantly alter the pharmacokinetics of the lithium, and no increase in adverse effects was noted. More longterm studies will be needed to confirm this lack of interaction, especially in patients with impaired renal function as both drugs are eliminated by renal excretion. ... 

Lai R, Sukbuntherng J, Luo W, Vicente V, Blumenthal R, Ho J, Cundy KC. Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine. Br J Clin Pharmacol 2010 69(5) 498-507. 

Lai R, Sukbuntherng J, Luo W, Huff FJ, Zou J, Cundy KC. The effect of food with varying fat content on the clinical pharmacokinetics of gabapentin after oral administration of gabapentin enacarbil. Int J Clin Pharmacol Ther 2010 48(2) 120-8. 

The bio availability of gabapentin is approximately 60%, 47%, 34%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day given in three divided doses, respectively. The bioavailability is not dose-proportional (as the dose is increased, bioavailability decreases). In contrast, pregabalin offers a more linear pharmacokinetic profile over gabapentin and a consistent >90% bioavailability. Pregabalin may result in a shorter course of titration and quicker response in clinical application. 

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