摘要:

The pharmacokinetics and pharmacodynamics of codeine and its metabolites codeine glucuronide, morphine, and morphine glucuronide were assessed after the administration of a single 60 mg oral dose of codeine sulfate and a single 60 mg intravenous dose of codeine phosphate in six healthy volunteers and six patients on chronic hemodialysis. Plasma and urine drug and metabolite concentrations were determined by sensitive and specific RIA procedures. Pharmacodynamics were assessed by pupillometry and vital sign determinations. Codeine elimination half‐life and mean residence time were increased significantly in the hemodialysis group (18.69 ± 9.03 hours and 12.77 ± 7.09 hours, mean ± SD, respectively) compared with the healthy volunteer group (4.04 ± 0.60 hours and 3.90 ± 0.52 hours, respectively). The total body clearance and volume of distribution of codeine were not significantly different between groups. Peak concentrations, times to peak concentrations, and AUCs for the three metabolites were also not significantly different between the groups, in part as a result of significant interpatient variability in the hemodialysis group. Examination of pupillometry and vital sign data did not reveal clinically significant differences in pharmacodynamics between the groups. Adjustment of dosage regimen may be required in some patients with uremia receiving multiple‐dose codeine therapy.Clinical Pharmacology and Therapeutics(1988)43,63–71; doi:10.1038/c

ISSN:0009-9236    

DOI:10.1038/clpt.1988.12

年代:1988

数据来源: WILEY

摘要:

The efficacy of buprenorphine and methadone was compared in the outpatient detoxification of heroin addicts. Forty‐five patients were randomized to receive either sublingual buprenorphine or oral methadone under double‐dummy and double‐blind conditions to study the pharmacology of buprenorphine in a 90‐day detoxification protocol. The patients were administered either 2 mg buprenorphine or 30 mg methadone for 3 weeks followed by 4 weeks of dose reductions and 6 weeks of placebo medication. No significant between‐group differences were seen on measures of treatment retention, drug use, or symptom report. During the hydromorphone challenge, methadone attenuated opioid effects to a greater extent than did buprenorphine on both physiologic (pupil constriction) and self‐report measures. However, this did not result in greater abuse of illicit opioid drugs by subjects taking buprenorphine. The results of this clinical trial indicated that buprenorphine was acceptable to patients and as effective as methadone in the detoxification treatment of heroin addicts.Clinical Pharmacology and Therapeutics(1988)43,72–78; doi:10.103

ISSN:0009-9236    

DOI:10.1038/clpt.1988.13

年代:1988

数据来源: WILEY

摘要:

The effects of rheumatoid arthritis disease activity on the pharmacokinetics of the highly albumin‐bound nonsteroidal anti‐inflammatory drug naproxen were studied in six patients during chronic therapy. In the same patients, kinetics during active disease were compared with those in improvement. Active disease is commonly associated with hypoalbuminemia: 30 ± 4 gm/L vs. 41 ± 2 gm/L (mean ± SD) at the time of improvement. Total naproxen concentrations were significantly lower in active disease, together with a larger apparent volume of distribution (10.6 ± 1.8 L vs. 8.4 ± 1.3 L; P<0.05) and total body clearance (0.79 ± 1.8 L/hr vs. 0.59 ± 0.14 L/hr; P<0.001). Peak unbound naproxen concentrations were 29% ± 19% (P<0.05) lower at the time of improvement. The unbound clearance was found diminished during active disease (390 ± 277 L/hr) in comparison with improvement (488 ± 343 L/hr; P<0.05). Clinical implications of the alterations in naproxen kinetics induced by polyarticular inflammation in patients with rheumatoid arthritis are discussed.Clinical Pharmacology and Therapeutics(1988)43,79–85; doi:10.1

ISSN:0009-9236    

DOI:10.1038/clpt.1988.14

年代:1988

数据来源: WILEY

摘要:

Without the availability of objective measures of central neurologic dysfunction, neuroepidemiologic investigations of individuals exposed to psychoactive drugs and potential environmental and occupational neurotoxins are extraordinarily difficult, particularly when the central nervous system manifestations are subtle, diffuse, and limited to cognitive deficits. In an attempt to assess and quantitate psychomotor dysfunction, P‐300 event‐related potentials, Symbol Digit Test, Continuous Performance Test, and Finger Tapping Test were obtained from six subjects sequentially exposed to nitrous oxide at 0%, 10%, 20%, and 40%. With increasing concentration of N2O, there was prolongation of P‐300 latency and worsening of Continuous Performance Test and Symbol Digit Test performance; P‐300 amplitude and Finger Tapping Test performance were decreased by exposure to N2O. This study demonstrates a dose‐dependent reduction in P‐300 amplitude and prolongation of P‐300 latency in subjects in whom psychomotor impairment was induced by the acute administration of N2O.Clinical Pharmacology and Therapeutics(1988)43,86–90; doi:10.1

ISSN:0009-9236    

DOI:10.1038/clpt.1988.15

年代:1988

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1988)43,91–92; doi:10.1038/clpt.1988.

ISSN:0009-9236    

DOI:10.1038/clpt.1988.16

年代:1988

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1988)43,93–93; doi:10.1038/clpt.1988.

ISSN:0009-9236    

DOI:10.1038/clpt.1988.17

年代:1988

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1988)43,94–94; doi:10.1038/clpt.1988.

ISSN:0009-9236    

DOI:10.1038/clpt.1988.18

年代:1988

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1988)43,95–95; doi:10.1038/clpt.1988.

ISSN:0009-9236    

DOI:10.1038/clpt.1988.19

年代:1988

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1988)43,96–122; doi:10.1038/clpt.1988.

ISSN:0009-9236    

DOI:10.1038/clpt.1988.20

年代:1988

数据来源: WILEY