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T Cramond

Publications and source records attributed to T Cramond.

17 recordsLinked to original sources
PubMed1995

Pharmacokinetics and pharmacodynamics of oxycodone when given intravenously and rectally to adult patients with cancer pain.

The single-dose pharmacokinetics and pharmacodynamics of oxycodone administered by the intravenous and rectal routes were determined in 12 adult cancer patients with moderate to severe cancer pain (visual analog scale [VAS] score, approximately 5). Oxycodone was administered by the intravenous and rectal routes with open drug administration and a cross-over design. After single-dose intravenous administration (7.9 +/- 1.5 mg, mean +/- SD), the mean (+/- SD) terminal half-life was 3.4 h (+/- 1.1), the mean (+/- SD) plasma clearance was 45.4 L/h (+/- 10.1), and the mean (+/- SD) volume of distribution in the terminal phase was 3.0 L/kg (+/- 1.1). After rectal oxycodone (30 mg), the mean (+/- SD) absorption lag time was 0.52 h (+/- 0.29) and the mean (+/- SD) absolute bioavailability was 61.6% (+/- 30.2%). Intravenous oxycodone was associated with a rapid onset of pain relief (5-8 min) in contrast to the 0.5- to 1.0-h delay observed after rectal administration. However, rectal oxycodone provided analgesia of much longer duration (approximately 8-12 h) than did intravenous oxycodone (approximately 4 h). There were no significant differences (P > 0.05) in the incidence and severity of side effects between intravenous and rectal oxycodone. The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study emphasizes the need for individualized dosing regimens.

Administration, Rectal↗
PubMed1994

Characterization of non-conventional opioid binding sites in rat and human lung.

Indirect evidence suggests that nebulized morphine relieves dyspnoea and bronchoconstriction via opioid receptors within the lung. This study used equilibrium binding studies to characterize opioid binding sites in lung membrane preparations. [3H]Morphine and [3H]naloxone were incubated separately with homogenates of Wistar rat brain and lung, and human lung. Binding affinities for both morphine and naloxone in rat and human lung were two orders of magnitude lower than those in brain. However, opioid binding site densities in lung were up to 100 times greater than that in brain. The addition of Na+ or GTP to lung homogenate preparations caused atypical effects on opioid binding. Na+ (50 mM) decreased the specific binding of [3H]naloxone 50% viz-à-vis a 20% increase in binding in the brain. GTP (100 microM) caused a 200% increase in the apparent capacity of morphine binding in the lung compared with a marked decrease in binding in the brain.

Animals↗
PubMed1994

The excitatory effects of morphine-3-glucuronide are attenuated by LY274614, a competitive NMDA receptor antagonist, and by midazolam, an agonist at the benzodiazepine site on the GABAA receptor complex.

Administration of morphine-3-glucuronide (M3G) by the intracerebroventricular (i.c.v.) route in doses of 2-8 micrograms produced a marked dose-dependent behavioural excitation in adult Sprague-Dawley rats. When LY274614 (1-50 ng i.c.v.) or midazolam maleate (25-50 micrograms i.c.v.) was administered 20 min prior to a maximal excitatory dose of M3G (7 micrograms), all excitatory behaviours were reduced. In contrast, when LY274614 (200 ng i.c.v.) was given after M3G (7 micrograms), it did not reduce all of the excitatory behaviours. Since we have also shown in in vitro binding studies that M3G has very low affinity for the known binding sites on the N-methyl-D-aspartate (NMDA) and the gamma-amino-butyric acid (GABAA) receptor complexes (1), the results of this study suggest that the anti-convulsant compounds, LY274614 and midazolam, are functional antagonists of the excitatory effects of M3G. LY274614 (1-50 ng i.c.v.) and midazolam (25-50 micrograms i.c.v.) did not produce significant behavioural excitation and phenyclidine (PCP)-type effects were not observed. This contrasts with the NMDA receptor antagonists CGS19755 and MK801, where PCP-type effects have been reported to interfere with behavioural assessment. Morphine hydrochloride in a maximal analgesic dose (50 micrograms i.c.v.), did not reduce the excitation score of a maximal excitatory dose of M3G (7 micrograms), lending support to the view that M3G's excitatory effects are elicited through a non-opioid mechanism.

Akathisia, Drug-Induced↗
PubMed1994

Quantitation of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in plasma and cerebrospinal fluid using solid-phase extraction and high-performance liquid chromatography with electrochemical detection.

An original, sensitive, and specific high-performance liquid chromatographic (HPLC) assay was developed for the quantitation of morphine and its two major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), in human plasma and cerebrospinal fluid (CSF) and in rat plasma, using hydromorphone as the internal standard. Solid-phase extraction was used to separate morphine and its glucuronide metabolites from plasma constituents. Extraction efficiencies of morphine, M3G, and M6G from human plasma samples (0.5 ml) were 84, 87, and 88%, respectively. Extraction efficiencies of morphine, M3G, and M6G did not differ significantly (p > 0.05) between human plasma and CSF or rat plasma. Morphine, M3G, M6G, and hydromorphone were separated on a 10 mu C8 Resolve radially compressed cartridge using a mobile phase comprising methanol:acetonitrile:phosphate buffer, (0.0125M pH 7.5; 10:10:80), in which 11 mg/L of cetyltrimethylammonium bromide (cetrimide) was dissolved. Quantitation was achieved using a single electrochemical detector at ambient temperature (23 degrees C). Standard curves were linear over the ranges 0.020-2.190, 0.027-2.709, and 0.027-0.542 microM for morphine, M3G, and M6G, respectively. Lower limits of detection for morphine, M3G, and M6G in human plasma and CSF samples (0.5 ml) were 0.020, 0.027, and 0.027 microM, respectively. Corresponding lower limits of detection in rat plasma (0.1 ml) were 0.102, 0.135, and 0.135 microM, respectively. Intraassay precision for low and high concentrations of morphine, M3G, and M6G were < 23 and < 8% respectively. Similarly, interassay accuracy for low and medium concentrations of morphine, M3G, and M6G were < 17% and were < 9% for high concentrations.

Animals↗
PubMed1993

Intraventricular morphine for intractable pain of advanced cancer.

Among the most difficult pain management problems are those associated with advanced head and neck cancer, and those in which pain is midline, bilateral, or diffuse. The authors report effective control of intractable pain in 52 patients by injection of small doses of morphine via an Ommaya or a Cordis reservoir into the lateral cerebral ventricle. The technique is safe and effective. The reservoir is usually inserted under local analgesia so the method of pain relief is available to patients in whom general anesthesia would be difficult or contraindicated. The doses of morphine required to maintain analgesia remain remarkably low. Tolerance reported by other authors has not been a problem when preoperative assessment of the patient has been thorough. Maximum survival time has been 75 wk and another patient has lived 65 wk. Complications included two colonized reservoirs, one dislodged ventricular catheter, three blocked catheters, and one postoperative meningitis. For patients with diffuse midline or bilateral pain, or intractable pain associated with advanced head and neck cancer, the use of intraventricular morphine should be considered when satisfactory pain relief is not achieved with oral morphine or continuous subcutaneous infusion.

Aged↗
PubMed1992

Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer.

The single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone have been determined in patients with moderate to severe cancer pain. The mean +/- SD elimination half-life after single-dose administration of intravenous (4.6 mg to 9.1 mg) and oral (9.1 mg) oxycodone was 3.01 +/- 1.37 hours and 3.51 +/- 1.43 hours, respectively. After intravenous administration, the mean +/- SD volume of distribution was 211.9 +/- 186.6 L, and the mean +/- SD total plasma clearance was 48.6 +/- 26.5 L/hr. The mean absolute oral bioavailability of oxycodone was 87%, and the mean +/- SD volume of distribution after oral administration was 249.1 +/- 204.3 L. When administered orally as 10 mg oxycodone hydrochloride every 4 hours, there was no accumulation of oxycodone at steady state and the mean +/- SD steady-state concentration was 34.6 +/- 10.3 micrograms/L. Intravenous oxycodone produced a faster onset of pain relief than oxycodone tablets, but the duration of analgesia was approximately the same (4 hours). However, the incidence of side effects and their severity were significantly higher (p < 0.05) for intravenous oxycodone than for oxycodone tablets. The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study supports the need for individualized dosing regimens.

Administration, Oral↗
PubMed1992

Comparative oxycodone pharmacokinetics in humans after intravenous, oral, and rectal administration.

The pharmacokinetics of oxycodone have been determined after single-dose administration by the intravenous (4.6-7.3 mg), oral (tablets, 9.1 mg and syrup, 9.1 mg), and rectal (30 mg) routes, in 48 patients undergoing minor surgery. There were no significant differences in the mean elimination half-lives between the intravenous (5.45 +/- 1.43 h), oral tablets (5.65 +/- 1.13 h), oral syrup (4.80 +/- 1.13 h), and rectal suppository (5.40 +/- 1.19 h) formulations of oxycodone. After intravenous administration, the mean plasma clearance of oxycodone was 25.5 +/- 10.1 L/h and the mean volume of distribution at steady state was 2.5 +/- 0.8 L/kg. The mean normalized area under the curve (AUC/D) obtained after intravenous dosing (48.2 +/- 30.2 micrograms.h/L/mg) was more than twice the AUC/D values obtained after the administration of oxycodone tablets (19.8 +/- 3.5 micrograms.h/L/mg), oxycodone syrup (17.5 +/- 5.3 micrograms.h/L/mg), and rectal suppository (20.3 +/- 5.1 micrograms.h/L/mg), indicating that the amount of oxycodone reaching the systemic circulation after the extravascular routes of administration was < 50% of that obtained after intravenous dosing. The mean absorption lag times after oxycodone tablets (0.52 +/- 0.33 h), oxycodone syrup (0.48 +/- 0.40 h), and rectal suppository (0.76 +/- 0.47 h) were consistent with the onset of pharmacological effects reported by the patients.

Administration, Oral↗
PubMed1991

Quantitation of oxycodone in human plasma using high-performance liquid chromatography with electrochemical detection.

An original, highly sensitive and specific high-performance liquid chromatographic (HPLC) assay has been developed for the measurement of oxycodone in human plasma with a detection limit of 10 ng/ml using a 1.0-ml plasma sample. Plasma samples were initially acid-washed and then extracted twice at pH 10 with butyl chloride. Oxycodone and codeine (internal standard) were eluted with a mixture of methanol, acetonitrile, and 0.01 M pH 7 phosphate buffer to which 40 mg/l of cetyltrimethylammonium bromide (cetavlon) was added at ambient temperature and detected with electrochemical detection. The addition of cetavlon to the mobile phase markedly reduced the interaction between oxycodone and Si-OH groups on the stationary phase of the HPLC column, so that the organic content of the mobile phase could be reduced from 80 to 25%. Quantitation was achieved using the peak height ratio of oxycodone to codeine. The assay is currently being used for the study of oxycodone pharmacokinetics after single oral doses of 10 and 20 mg and single rectal doses of 30 mg.

Administration, Oral↗
PubMed1990

Morphine-3-glucuronide--a potent antagonist of morphine analgesia.

In this study, morphine-3-glucuronide (M3G), the major plasma and urinary metabolite of morphine, was shown to be a potent antagonist of morphine analgesia when administered to rats by the intra-cerebroventricular (i.c.v.) route. The antagonism of morphine analgesia was observed irrespective of whether i.c.v. M3G (2.5 or 3.0 micrograms) was administered 15 mins prior to or 15 mins after i.c.v. morphine (20 micrograms). When M3G (10mg) was administered intraperitoneally (i.p.) to rats 30-40 mins prior to morphine (1.5mg i.p.), the analgesic response was significantly reduced compared to administration of morphine (1.5mg i.p.) alone. It was further demonstrated that i.c.v. M3G (2.0 micrograms) antagonized the analgesic effects of subsequently administered i.c.v. morphine-6-glucuronide (0.25 micrograms).

Analgesia↗
PubMed1986

The Combibag: an evaluation of a new self-inflating resuscitator.

The Combibag self-inflating resuscitator incorporates an adult and a paediatric segment as well as a two-stage pressure-limiting safety valve. The resuscitator is not without problems. A sizeable forward leak of gas can occur beyond the patient valve. The patient valve design is such that a spontaneously breathing patient draws his inspired gas entirely from room air. Problems can also occur with the valve either sticking or being blown forward off its seating, thereby making the resuscitator inoperable and dangerous. The use of a two-stage pressure-limiting safety valve should prevent unnecessary barotrauma but could well lead to unrecognised venting with inadequate ventilation when used by inexperienced personnel.

Adult↗
PubMed1985

Resusciaide.

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Acquired Immunodeficiency Syndrome↗