Methods and findings in experimental and clinical pharmacology
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Cytidine 5'-diphosphocholine, CDP-choline or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine. Upon oral or parenteral administration, CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. ⋯ Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease. No serious side effects have been found in any of the groups of patients treated with CDP-choline, which demonstrates the safety of the treatment.
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Methods Find Exp Clin Pharmacol · Jan 1995
Comparative Study Clinical TrialComparison of bioimpedance and Doppler ultrasound cardiac output in CAPD patients.
The reproducibility and reliability of cardiac output (CO) measurement by transthoracic electrical bioimpedance (TEB) and dual beam Doppler ultrasound methods were compared in 9 uremic patients during treatment with continuous ambulatory peritoneal dialysis (CAPD). CO was measured simultaneously by each method during supine rest and 70 degree passive head-up tilt on two separate days. The effect on CO after the infusion of dialysate was also studied on day 1. ⋯ CO and SV measured by Doppler were higher than that by TEB during supine rest (p < or = 0.01) but not during passive tilt. As a result, there was significant change (p < or = 0.01) in CO and SV from supine to tilt measured by Doppler but not by TEB. Neither TEB nor Doppler detected significant change (p > 0.05) in CO or SV after the infusion of dialysate, in either the supine or tilt positions.(ABSTRACT TRUNCATED AT 250 WORDS)
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Methods Find Exp Clin Pharmacol · Sep 1994
ReviewSelective activation of anticancer prodrugs by monoclonal antibody-enzyme conjugates.
Several recent reports have demonstrated that anticancer drugs can be generated site-selectively at solid tumors by monoclonal antibody-enzyme conjugates targeted to antigens on tumor cell surfaces. The first step in this drug targeting approach involves the delivery of the enzyme conjugate to a tumor cell population. After the conjugate has localized within the tumor and cleared from non-target tissues, a relatively non-cytotoxic drug precursor (prodrug) is administered. ⋯ In another example involving targeted cytosine deaminase for the generation of 5-fluorouracil, it is shown that as much as 17 times more drug can be delivered within a tumor compared to when 5-fluorouracil is administered alone. The method of using targeted enzymes for prodrug activation can be extended to include prodrugs that release very potent drugs, such as palytoxin, a marine natural product, and to treat cells that have the multidrug resistance phenotype. Some of the requirements for successful therapy with this approach for cancer therapy are discussed.
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Methods Find Exp Clin Pharmacol · Apr 1994
Antinociceptive effects of ketamine-opioid combinations in the mouse tail flick test.
The antinociceptive activities of intraperitoneal (i.p.) ketamine in combination with subcutaneous (s.c.) morphine or fentanyl were studied using the mouse tail flick test, an acute pain model. Morphine and fentanyl exhibited dose-dependent effects, with respective ED50s (95% confidence limits) of 1.3 (1.2-1.4) mg/kg and 6.8 (6.2-7.4) mcg/kg. Ketamine (1, 5, 10 and 20 mg/kg) showed relatively weak antinociceptive effects with no apparent dose-response relationship. ⋯ Fentanyl (0.5 mcg/kg) pretreatment significantly enhanced ketamine (20 mg/kg) activity, with no apparent effect on ketamine 10 mg/kg. At 2.5 mcg/kg, fentanyl pretreatment significantly enhanced ketamine antinociception. These results suggest that ketamine may not be as effective in acute pain as opioids are, and that after systemic administration, the net effect of ketamine-opioid combination is a simple additive one.
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Methods Find Exp Clin Pharmacol · Sep 1993
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialEfficacy of two different intramuscular doses of dipyrone in acute renal colic. Cooperative Study Group.
A randomized multicenter clinical trial was designed to compare the efficacy and tolerance of two different intramuscular doses of dipyrone (1 g and 2 g) with those of the reference drug, diclofenac sodium (75 mg), in the treatment of acute renal colic. A total of 129 patients were included; 43 patients were alloted to receive dipyrone 1 g, 45 to dipyrone 2 g, and 41 to diclofenac. ⋯ There were no significant differences between the three groups in terms of pain relief in the first 60 min, but dipyrone 2 g provided significantly more pain relief than diclofenac and dipyrone 1 g from 60 min to 6 h after drug injection. It is concluded that dipyrone 2 g produced a longer lasting analgesic response than dipyrone 1 g in the treatment of renal colic.