Gabapentin and pregabalin are calcium channel antagonists, blocking the release of neurotransmitters. These medications are indicated in the treatment of neuropathic pain, including diabetic peripheral neuropathy, postherpetic neuralgia, central neuropathic pain and fibromyalgia. They have also been shown to be beneficial analgesic adjuncts in a number of operative settings.
Despite the same mechanism of action, gabapentin and pregabalin have differing pharmacokinetic profiles, which alter effective dosing regimens. Following oral administration, gabapentin has zero-order absorption and its bioavailability varies from approximately 60% at a total daily dose of 900mg to only 33% at doses up to 3600mg per day. Pregabalin follows a linear absorption pattern with a bioavailability of over 90% at all doses. Both gabapentin and pregabalin have a half-life of 6 hours and primarily undergo renal excretion. This indicates that increasing doses of pregabalin will likely produce more predictable changes in pain improvement.
Serpell et al, conducted a gabapentin dosing study with an initial total daily dose of 300mg, divided into three doses, and titrated up to a total daily dose of 900mg per day over the course of 3 days. There were minimal side effects for most patients at this dosing level. For patients who reported an improvement in pain at 900mg per day, further titration was increased over the course of 5 weeks to 2400mg per day. Patients receiving gabapentin showed a statistically significant improvement in pain scores compared to placebo with only mild to moderate side effects reported. The maximum recommended dosing for gabapentin is currently 3600mg per day.
Additionally, Freynhagen et al, investigated pregabalin dosing and determined that doses ranging from 150-600mg per day provided statistically significant improvement in pain scores. Patients were started at 150mg per day divided into two doses and titrated weekly based on response and tolerability. The study showed a low dropout rate due to side effects. The current maximum dose of pregabalin is 600mg per day.
Due to primary renal excretion with both gabapentin and pregabalin, dosing should be reduced based on creatinine clearance with additional doses given after hemodialysis.
References:
- Serpell MG. Gabapentin in neuropathic pain syndromes: a randomized, double blind, placebo-controlled trial. Pain 2002; 99(3): 557-566.
- Freynhagen R, Strojek K, Griesing T, et al. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomized, double blind, multicenter, placebo-controlled trial of flexible-and fixed dose regimens. Pain 2005; 115(3): 254-63.
- Moore RA, Wiffen PJ, Derry S, et al. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2014; 27(4).
- Moore RA, Straube S, Wiffen PJ, et al. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev 2009; 8(3).