Data BDIX SD Carprofen Refinement

Data concerning the following project/manuscript:

Perioperative dose intake and plasma concentrations achieved with pain therapy based on voluntary carprofen intake depend on rat strain and surgical procedure

Aylina Glasenapp, Alina Ottlewski, Marcel Oelerich, Mesbah Alam, Christine Häger, Heike Bähre, Kerstin Schwabe, Marion Bankstahl

Introduction: Surgical interventions in rats require appropriate pain relief. Based on previous species-specific pharmacokinetic and safety evaluations, this study investigated refined carprofen-based multimodal analgesic regimens for surgical interventions in two rat strains. Methods: Male rats (BDIX, n=14; Sprague Dawley (SD), n=6) underwent subcutaneous (s.c.) transmitter implantation (TM) and up to two consecutive neurosurgeries (tumor cell injection, BDIX; intracerebral 6-OHDA injection and electrode implantation, SD). Analgesia was based on voluntary intake of carprofen-medicated water (10 mg/kg/24 h) starting either after (regimen 1) or before (regimen 2) surgery and continuing for three days post intervention. This was combined with a single s.c. injection of carprofen (5 mg/kg) before (regimen 1, BDIX) or after (regimen 2, BDIX, SD) surgery as well as intraoperative local anesthesia. At expected critical time points (12, 24, 36 h post surgery), plasma concentrations were measured. Water intake, body weight, and clinical scores were recorded daily. Results: Analgesic regimen 1 did not achieve the desired plasma levels in most individuals due to reduced water intake and consequent failure of target dose intake. With regimen 2, carprofen-medicated water intake before surgery was reduced in BDIX but increased in SD rats. Following s.c. TM and frontal tumor cell injection in BDIX, as well as after intracerebral 6-OHDA injection in SD rats, plasma levels reflected transiently decreased water intake. Still, regimen 2 resulted in anticipated plasma levels for up to 36 h post surgery, depending on the intervention type. Bodyweight was marginally reduced after all surgery types in BDIX and increased after transmitter implantation in SD rats. Clinical score values increased in several SD rats after 6-OHDA injection, reflecting the loss of nigrostriatal dopamine, as well as after electrode implantation. Discussion: Voluntary oral carprofen intake was influenced both by rat strain and surgery type. When oral treatment started in the pre-operative phase target plasma levels were generally achieved even at critical time points, particularly after TM. As water consumption might be reduced early after interventions, monitoring fluid intake is recommended for non-invasive carprofen treatment. Should fluid intake be distinctly reduced, an additional carprofen injection on day 2 post surgery may be beneficial.