Pharmacokinetic and pharmacodynamic studies of pregabalin suppositories based on pharmacological research

Abstract

Objectives As commercially available pregabalin preparations are limited to oral administration, it is impossible to use it as an adjuvant analgesic for neuropathic cancer‐related pain in terminally ill cancer patients with oral feeding difficulties. The objective of this study was to develop a pregabalin suppository to be available at hospitals. Methods Pregabalin suppositories were prepared using bases comprising six different compositions of Witepsol H‐15, Witepsol S‐55, and Witepsol E‐75. The suppository release test and stability test were performed in vitro. The pharmacokinetics and pharmacodynamics of the suppositories were assessed in rats. Key findings In the in vitro releasing test, the pregabalin suppositories with H‐15, H‐15 : S‐55 = 1 : 1, H‐15 : S‐55 = 2 : 1, H‐15 : S‐55 = 1 : 2 released approximately 100% of the pregabalin within 180 min. Among these pregabalin suppositories, only the suppository with H‐15 : S‐55 = 2 : 1 demonstrated an equivalent AUC0−∞ with the oral administration group. Consistent with the results of the pharmacokinetic study, the pregabalin suppository with H‐15 : S‐55 = 2 : 1 exhibited antinociceptive effects. In addition, the pregabalin suppository with H‐15 : S‐55 = 2 : 1 was stable for 12 weeks when refrigerated with light shielding. Conclusions The pregabalin suppositories prepared in this study may be applicable for pain control for terminally cancer ill patients with oral feeding difficulties.

Successful use of Rectal Pregabalin for the Treatment of Chemotherapy-Induced Neuropathic Pain—a Case Report

“…Based on the available evidence we decided to start a treatment attempt with pregabalin given rectally. 2,3 Thereupon, we contacted our pharmacy with the request to produce a rectal application form of pregabalin in accordance with current literature. 2,3 Suppositories were prepared from pregabalin capsules (Pregabalin 300 mg, PUREN Pharma GmbH & Co. KG, Germany) and the base hard fat W 35 (Fagron GmbH & Co. KG, Germany).…”

“…2,3 Thereupon, we contacted our pharmacy with the request to produce a rectal application form of pregabalin in accordance with current literature. 2,3 Suppositories were prepared from pregabalin capsules (Pregabalin 300 mg, PUREN Pharma GmbH & Co. KG, Germany) and the base hard fat W 35 (Fagron GmbH & Co. KG, Germany). The suppositories were produced following the Münzel-Method.…”

“…4 The base described in the literature is little used and has poor commercial availability in Germany. 2 The patient was informed about the off-label drug use, to which she consented. According to the described data, our target dose with pregabalin was 1.5 the previous oral dose because of the presumably reduced rectal bioavailability.…”

“…According to the described data, our target dose with pregabalin was 1.5 the previous oral dose because of the presumably reduced rectal bioavailability. 2 We decided on a gradual dose titration and increased the dose over three days until the target dose of 150 mg administered twice a day was reached. Under this, the patient reported a significant reduction in tingling paresthesias after only two days (Figure 1).…”

Preclinical Evaluation of Polymeric Nanocomposite Containing Pregabalin for Sustained Release as Potential Therapy for Neuropathic Pain

“…Some studies have proposed modified-release pharmaceutical formulations containing PG for once-daily administration, such as transdermal delivery of PG [9]; PG microspheres [10][11][12]; PG formulations with longer stomach duration [6,[13][14][15][16][17][18][19][20]; and PG suppository [21]. The treatment of neuropathic pain has been the focus of several of these formulations.…”