General Description

Gabapentin, with its straightforward pharmacokinetics characterized by renal excretion and linear elimination kinetics, is a valuable asset in dermatology. It is effective in managing neuropathic conditions like postherpetic neuralgia, neuralgias in various body areas, and pruritus. The medication's mechanism of action involves inhibiting calcium ion channels and enhancing GABA synthesis. Gabapentin also shows promise in treating chronic pain syndromes, allodynia, and reflex sympathetic dystrophy. The recommended dosage of Gabapentin typically starts at 300 mg daily, gradually increasing to 1200 mg thrice daily. Adherence to prescribed dosages and gradual tapering during discontinuation are crucial for optimal therapeutic outcomes.

Figure 1. Gabapentin

Pharmacokinetics

Gabapentin have undergone extensive research to determine their absorption, distribution, metabolism and elimination properties. Gabapentin immediate-release formulations readily disintegrate; the drugs are highly soluble in aqueous media. Doses of the capsule and tablet formulations are bioequivalent to solution doses. The system-L transporter family facilitates large, neutral, amino acid transport (LAT), including phenylalanine, leucine, isoleucine and valine,  as well as intestinal absorption of pregabalin. Preclinical studies have suggested that gabapentin is transported solely by the LAT1 transporter, resulting in dose-limited absorption, presumably because of saturation of the facilitated transport process. 

The rate of gabapentin absorption is relatively slow, with peak plasma concentrations occurring around 3 hours postdose. The rate and extent of absorption are influenced by the absence or presence of the transporter(s) along the gastrointestinal tract, which facilitates the passage of each of these compounds from the intestinal lumen to the systemic circulation. Colonic intubation studies have indicated that systemic absorption of gabapentin occurs primarily in the small intestine, with minimal absorption in the colon, which limits gabapentin absorption. In addition to absorption in the small intestine, colonic intubation studies have indicated that pregabalin absorption extends into the ascending portion of the colon.¹

Clinical Uses

Approximately 10–15% of herpes zoster patients will develop postherpetic neuralgia, which can persist for many years. Dermatologists are often the primary care providers for postherpetic neuralgia patients. Several trials conducted previously reported statistically significant reduction in average daily pain after gabapentin and pregabalin. Gabapentin is the first oral medication approved in the USA for this condition. Reviews of controlled studies showed that patients suffering from postherpetic neuralgia experienced a statistically significant reduction in average daily pain after treatment with gabapentin. The study also showed that those receiving gabapentin experienced improvement in sleep and overall quality of life. Gabapentin is useful in the treatment of neuralgia in all areas of the body. Its positive effect on neuralgia includes trigeminal neuralgia, glossopharyngeal neuralgia refractory to the usual medical treatments and facial neuritis. It is also useful in treating inflammatory pain. Gabapentin is also effective in the treatment of human immunodeficiency virus (HIV) neuropathy, painful diabetic neuropathy and diabetic neuropathic pain. Of particular interest to dermatologist is the probable usefulness of this drug in decreasing the trophic ulcerations that results from neuropathy in diseases such as HIV, leprosy and diabetes that are prone to such ulcers. Pregabalin is found to be efficacious in treating Red scrotum syndrome (poorly understood, chronic dysesthetic erythema primarily involving the anterior scrotum).²

Reference

1. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010; 49(10): 661-669.

2. Mittal A, Agarwal C, Balai M, Taneja A. Gabapentin and pregabalin in dermatology. Indian J Dermatol Venereol Leprol. 2018; 84(5): 634-640.