Pharmacokinetics, pharmacodynamics, and analgesic effects of morphine after rectal, intramuscular, and intravenous administration in dogs

OBJECTIVE: To compare systemic bioavailability and duration for therapeutic plasma concentrations and cardiovascular, respiratory, and analgesic effects of morphine administered per rectum, compared with IV and IM administration in dogs. ANIMALS: 6 healthy Beagles. PROCEDURE: In a randomized study, each dog received the following: morphine IV (0.5 mg/kg of body weight), morphine per rectum (1, 2, and 5 mg/kg as a suppository and 2 mg/kg as a solution), and a control treatment. Intramuscular administration of morphine (1 mg/kg) was evaluated separately. Heart and respiratory rates, systolic, diastolic, and mean blood pressures, adverse effects, and plasma morphine concentrations were measured. Analgesia was defined as an increase in response threshold, compared with baseline values, to applications of noxious mechanical (pressure) and thermal (heat) stimuli. Data were evaluated, using Friedman repeated-measures ANOVA on ranks and Student-Newman-Keuls post-hoc t-tests. RESULTS: Significant differences were not found in cardiovascular, respiratory, or analgesia values between control and morphine groups. Overall systemic bioavailability of morphine administered per rectum was 19.6%. Plasma morphine concentration after administration of the highest dose (5 mg/kg) as a suppository was significantly higher than concentrations 60 and 360 minutes after IV and IM administration, respectively. A single route of administration did not consistently fulfill our criteria for providing analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Rectal administration of morphine did not increase bioavailability above that reported for oral administration of morphine in dogs. Low bioavailability and plasma concentrations limit the clinical usefulness of morphine administered per rectum in dogs.     

Extraction and cleanup procedures for determination of diarylphosphates in fish, sediment, and water samples

Methods for determination of triaryl/alkylphosphates (TAPs) in water, fish, and sediment have been extended to determination of the diarylphosphate (DAP) degradation products. DAPs were extracted from water (adjusted to pH 0.5) by use of XAD-2 resin and determined by gas-liquid chromatography as butyl esters. Recovery of diphenylphosphate (DPP) and o-, m-, p-dicresylphosphates (DoCP, DmCP, DpCP) were greater than 95% in water samples fortified at 1, 10, and 50 micrograms/L. DAPs were extracted from fish with methanol and the extracts were cleaned up on reverse phase (C18) silica cartridges. Recoveries were greater than 87% for DPP, DoCP, DmCP, and DpCP in fish muscle fortified at 50, 100, and 500 ng/g. Sediments were refluxed with aqueous methanol and DAPs were recovered by use of XAD-2 resin. Recoveries of DAPs from sediments fortified at 50 and 100 ng/g were greater than 76%. Interferences (1-10 ng/g) from phosphorus or nitrogen-containing GLC peaks prevented sub- ng/g level analysis for DAPs in sediment and fish extracts.     

Respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution in endotoxemic calves

The respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution (HSS) treatment were examined in 12 endotoxic, pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli endotoxin (055:B5) was infused IV at a rate of 0.1 microgram/kg of body weight over 30 minutes. Endotoxin induced severe respiratory effects, with marked hypoxemia and increases in arterial-alveolar O2 gradient (P[A-a]O2), physiologic shunt fraction (Qs/Qt), and physiologic dead space to tidal volume ratio (Vd/Vt). Oxygen consumption was decreased, despite an increase in the systemic O2 extraction ratio. Peak effects were observed at the end of endotoxin infusion. The renal response to endotoxemia was characterized by a decrease in free-water reabsorption and osmotic clearance, as well as a decrease in sodium and phosphorus excretion. Endotoxemia induced leukopenia, thrombocytopenia, hyperphosphatemia, hypoglycemia, acidemia, and increased serum alkaline phosphatase concentrations. Calves were treated with HSS (2,400 mosm/L of NaCl, 4 ml/kg, n = 4) or an equivalent sodium load of isotonic saline solution (ISS; 300 mosm/L of NaCl, 32 ml/kg, n = 4 90 minutes after the end of endotoxin administration. Both solutions were infused over a 4- to 6-minute period. A control group (n = 4) was not treated. Infusion of HSS or ISS failed to induce a significant change in Pao2, P(A-a)O2, (Qs/Qt), (Vd/Vt), or oxygen consumption. Both solutions increased systemic oxygen delivery to above pre-endotoxin values. Hypertonic saline infusion induced significant (P less than 0.05) increases in serum Na and Cl concentrations and osmolality, whereas ISS induced a significant increase in serum Cl concentration and a significant decrease in serum phosphorus concentration.(ABSTRACT TRUNCATED AT 250 WORDS)