Intravenous administration of paclitaxel in Sprague‐Dawley rats: what is a safe dose?

Abstract

Few studies describe the administration of Taxol to rats; however, rats are typically used to study the toxicity of new drugs or novel formulations. A dose finding study was conducted to determine a safe dose of Taxol following intravenous administration in rats. Male Sprague-Dawley rats received a bolus of paclitaxel 5-20 mg/kg i.v. Blood was drawn before administration and at the following times after administration: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 h. Plasma concentrations were determined using high performance liquid chromatography. Two rats received paclitaxel 20 mg/kg and died immediately. Nine rats received paclitaxel 10 mg/kg; seven of these rats died within 12 h and two rats were killed due to moribund conditions. Ten rats received paclitaxel 5 mg/kg with no morbidity. The following pharmacokinetics for paclitaxel in the plasma were estimated: C0, 8977 ng/ml; AUC(0 --> infinity), 7477 ng*h/ml; CL(s), 668 ml/h*kg; V(ss), 1559 ml/kg; V(z) 2557 ml/kg and t(1/2), 2.6 h. It is concluded that further pharmacokinetic studies that are rationally designed to include appropriate measures of preclinical toxicity associated with paclitaxel are needed to identify formally the safest dose in rats following intravenous administration; however, these data indicate that male Sprague-Dawley rats can safely receive Taxol in a 5 mg/kg i.v. bolus.

Preparation and Evaluation of PEGylated and Folate‐PEGylated Liposomes Containing Paclitaxel for Lymphatic Delivery

“…administration. A single dose (5 mg/kg as Ptx) of each Ptx formulation was given to rats intravenously at the same time [40]. At predetermined time intervals (0.083, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, and 12 hours), whole blood samples (about 350 L) were withdrawn via the femoral artery into a Vacutainer tube with EDTA.…”

Subharmonic-Aided Pressure Estimation for Monitoring Interstitial Fluid Pressure in Tumors: Calibration and Treatment with Paclitaxel in Breast Cancer Xenografts

“…Moreover, there were no significant changes in IFP between days and no significant changes pre to post treatment. Paclitaxel is more toxic to rats than to humans and the dose given was only 25% of what is normally used in humans (5 vs. 20 mg/kg) as that is the highest safe paclitaxel dose for rats (Shord & Camp 2006). This might also have contributed to the lack of effect from the chemotherapy.…”

“…SHAPE and the Stryker pressure monitor measurements were performed before (on day 21, 24 or 28) and 48 hours after administration of a single IV injection in a lateral tail vein of 5 mg/kg of paclitaxel. The paclitaxel dosage (5 mg/kg) was selected based on a study by Shord and Camp (2006). Additionally, tumor volumes were measured with a caliper every other day to allow growth curves to be established and compared.…”

Pharmacokinetic profile of paclitaxel in the plasma, lung, and diaphragm following intravenous or intrapleural administration in rats

“…Previous pharmacokinetic studies have administered intravenous paclitaxel doses ranging from 5 mg/kg–15 mg/kg to rats. 15 , 20 However, the safest dose of paclitaxel for intravenous use in rats is reported to be less than 5 mg/kg. 15 Therefore, to minimize potential toxicity for the animals, the dose of 3 mg/kg was established.…”

“…One hundred and twenty rats were randomly divided into two equal groups ( n = 60). Rats received 3 mg/kg paclitaxel 15 either intravenously in the tail vein (group I) or in the pleural cavity (group II) at the same dose. In group II, after anesthetization with ether, a small (1–2 mm) incision in the right thoracic wall of the rats was opened and the drug was injected into the pleural cavity using a smoothly polished blunt syringe, at a depth of 1 cm.…”