Assessment of in vitro release of carboplatin from six carrier media.

OBJECTIVE To investigate in vitro carboplatin release from 6 carrier media. SAMPLE 6 carboplatin-containing carrier media. PROCEDURES An in vitro release study was performed with 6 commercially available carrier media: a hemostatic gelatin sponge, a poloxamer copolymer gel, and 2 sizes (3 and 4.8 mm in diameter) of beads molded from each of 2 commercial calcium sulfate products. All carrier media contained 10 mg of carboplatin. Carrier media specimens were placed in 37°C PBS solution for 96 hours. Carboplatin concentrations in PBS solution were measured by use of high-performance liquid chromatography at 15 time points to calculate the amount and proportion of carboplatin released from each specimen. RESULTS Peak release of carboplatin from the poloxamer copolymer gel and hemostatic gelatin sponge were achieved after 4 and 20 hours, respectively. Maximum release did not differ significantly between the poloxamer copolymer gel and hemostatic gelatin sponge, but both released significantly more carboplatin within 96 hours than did both of the commercial calcium sulfate products. The poloxamer copolymer gel released 99% of the carboplatin, and the hemostatic gelatin sponge released 68.5% of the carboplatin. Peak release of carboplatin from the calcium sulfate beads was not reached within 96 hours. CONCLUSIONS AND CLINICAL RELEVANCE In this study, carboplatin release from the hemostatic gelatin sponge was incomplete. The poloxamer copolymer gel and hemostatic gelatin sponge released carboplatin rapidly in vitro, whereas calcium sulfate beads did not.

Ronidazole pharmacokinetics after intravenous and oral immediate-release capsule administration in healthy cats.

Ronidazole (RDZ) is an effective treatment for feline Tritrichomonas foetus infection, but has produced neurotoxicity in some cats. An understanding of the disposition of RDZ in cats is needed in order to make precise dosing recommendations. Single-dose pharmacokinetics of intravenous (IV) RDZ and immediate-release RDZ capsules were evaluated. A single dose of IV RDZ (mean 9.2mg/kg) and a 95mg immediate-release RDZ capsule (mean 28.2mg/kg) were administered to six healthy cats in a randomized crossover design. Plasma samples were collected for 48 h and assayed for RDZ using high pressure liquid chromatography (HPLC). Systemic absorption of oral RDZ was rapid and complete, with detection in the plasma of all cats by 10 min after dosing and a bioavailability of 99.64 (±16.54)%. The clearance of RDZ following IV administration was 0.82 (±0.07) ml/kg/min. The terminal half-life was 9.80 (±0.35) and 10.50 (±0.82) h after IV and oral administration, respectively, with drug detectable in all cats 48h after both administrations. The high oral bioavailability of RDZ and slow elimination may predispose cats to neurotoxicity with twice-daily administration. Less frequent administration should be considered for further study of effective treatment of T foetus-infected cats.

Evaluation of intermittent infusion of bupivacaine into surgical wounds of dogs postoperatively.

Thirty-one dogs were randomised to receive intermittent wound infusion of bupivacaine or saline after surgery. Wound pressure sensitivity, pain scores, body temperature, heart rate, respiratory rate, analgesic drugs administered, time to walking and time to eating after surgery were recorded. Plasma bupivacaine concentrations were measured. The relative frequency distributions of the non-interventional and interventional pain scores, but not the relative frequency distributions of palpation pain scores or wound pressure sensitivity, were significantly different between groups following surgery. There was a significant difference between groups in the time to eating and in the amount and timing of analgesic drugs administered. Measured plasma bupivacaine concentrations demonstrated systemic absorption of the drug. Bupivacaine infusion into surgical wounds after surgery may improve post-operative recovery, but no effect on wound tenderness was demonstrated in this study.

Evaluation of a midhumeral block of the radial, ulnar, musculocutaneous and median (RUMM block) nerves for analgesia of the distal aspect of the thoracic limb in dogs.

OBJECTIVE: To evaluate a technique for midhumeral peripheral nerve blockade in the dog. STUDY DESIGN: Cadaveric technique development; in vivo placebo-controlled, prospective crossover study. ANIMALS: Canine cadavers (n=38) and 8 clinically healthy, adult hound dogs. METHODS: A technique for peripheral block of the radial, ulnar, musculocutaneous, and median nerves (RUMM block) was evaluated using cadaver limbs. Eight purpose-bred, research dogs were anesthetized; a RUMM block was performed on each thoracic limb. One limb from each dog randomly received 0.5% bupivacaine and the opposite limb was assigned to receive sterile saline solution as a control. After recovery from anesthesia, skin sensation at selected dermatomes was evaluated for 24 hours using a mechanical stimulus. Weight-bearing, conscious proprioception, and withdrawal reflex were also evaluated. One month after initial testing, each dog was reanesthetized and each limb received the opposite treatment. RESULTS: Sensory thresholds were significantly increased over baseline measurements when compared with control limbs for all nerves. Complete sensory block was achieved in radial (15/16), ulnar (3/16), musculocutaneous (8/16), and median (11/16) nerves, using a mechanical stimulus of analgesia. Complete simultaneous block of all nerves was only obtained in 1 of 16 limbs. CONCLUSION: RUMM block resulted in desensitization of the skin in the associated dermatomes for 4-10 hours. Complete sensory block of the dermatomes supplied by the radial nerve was most consistent. CLINICAL RELEVANCE: RUMM block may be an effective technique to provide adjunctive analgesia for dogs undergoing surgery of the distal aspect of the thoracic limb.

Effects of compounding and storage conditions on stability of pergolide mesylate.

OBJECTIVE: To determine the effects of temperature and light over a 35-day period on stability of pergolide mesylate after compounding in an aqueous vehicle. DESIGN: Evaluation study. PROCEDURES: Pergolide was compounded into a formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at -20 degrees, 8 degrees, 25 degrees, or 37 degrees C without exposure to light or at 25 degrees C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 days of storage. RESULTS: Mean+/-SD concentration of pergolide in the formulation immediately after compounding was 1.05+/-0.086 mg/mL. Samples exposed to light while stored at 25 degrees C had undergone excessive degradation by day 14, samples stored at 37 degrees C had undergone excessive degradation by day 21, and samples stored at 25 degrees C without exposure to light had undergone excessive degradation by day 35. The decrease in expected concentration corresponded with the appearance of degradation peaks in chromatograms and with a change in color of the formulation. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that pergolide mesylate was unstable after compounding in an aqueous vehicle and that storage conditions had an effect on stability of the compounded formulation. Compounded pergolide formulations in aqueous vehicles should be stored in a dark container, protected from light, and refrigerated and should not be used >30 days after produced. Formulations that have undergone a color change should be considered unstable and discarded.