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Petter C Borchgrevink

Publications and source records attributed to Petter C Borchgrevink.

12 recordsLinked to original sources
PubMed2006

Long term methadone for chronic pain: a pilot study of pharmacokinetic aspects.

Methadone is used as an alternative opioid when first line opioids fail to provide adequate pain control. Highly variable morphine:methadone dose ratios make switching challenging and little is known about the pharmacokinetics of long lasting methadone treatment for pain. Twelve patients treated with morphine for chronic non-malignant pain were switched to methadone. Seven of these patients continued with methadone throughout the nine months study period and only minor dose adjustments were performed. Serum concentrations of morphine, methadone and their metabolites were measured at baseline, day one and two, after dose titration and one week, five weeks, three months and nine months after the end of dose titration. Serum concentrations of methadone and its metabolite EDDP did not change significantly from the end of dose titration and during the nine months (repeated measures ANOVA: p=0.88 and p=0.06). Very low correlation between dose ratios and serum concentration ratios between morphine and methadone was observed. Large interindividual differences in serum concentrations and metabolism were observed. Our findings contradict that autoinduction of methadone metabolism takes place during long term treatment and supports that a 3-day opioid switch from morphine to methadone followed by a one week titration seems pharmacologically sound.

Adult↗
PubMed2006

Opioid switching from morphine to methadone causes a minor but not clinically significant increase in QTc time: A prospective 9-month follow-up study.

Case reports and retrospective studies suggest that methadone causes an increase in QTc (QT time corrected for heart rate) time and risk of torsades de pointes arrhythmia. No prospective studies in pain patients have been conducted, and data on whether a methadone-induced increase in QTc time persists during long-term treatment have not been reported. Eight chronic nonmalignant pain patients experiencing insufficient pain control or intolerable side effects during treatment with oral morphine switched to oral methadone and were included in this study. Electrocardiograms were obtained at baseline and at follow-up 2 weeks, and 3 and 9 months after the opioid switch. Start of methadone caused a minor but statistically significant increase in QTc time, while fluctuations in QTc during treatment with stable doses of methadone were neither clinically nor statistically significant. We observed no episodes of arrhythmias.

Aged↗
PubMed2005

[Genetic variation-- important for the clinical effect of opioids?].

The individual variability of opioid pharmacology suggests that the patients' genetic disposition influences the response to opioids. Given the complexity of morphine pharmacology, variability may be caused by several genes. Data suggest that variability in genes encoding the enzyme metabolising morphine (UGT2B7 gene), mu-opioid receptors (OPRM1 gene) and BBB transport of morphine by multidrug resistance transporters (MDR1 gene) influence the clinical efficacy of morphine. Furthermore, variability in an enzyme-degrading catecholamines (COMT gene) may also alter the efficacy of morphine, which shows that genetic variability in non-opioid systems may indirectly influence the clinical opioid efficacy. Results obtained so far strongly suggest that opioid efficacy is partly related to inborn properties caused by genetic variability.

Analgesics, Opioid↗
PubMed2004

Day-to-day variations during clinical drug monitoring of morphine, morphine-3-glucuronide and morphine-6-glucuronide serum concentrations in cancer patients. A prospective observational study.

BACKGROUND: The feasibility of drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. One important factor relevant to drug monitoring is to what extent morphine, M6G and M3G serum concentrations fluctuate during stable morphine treatment. METHODS: We included twenty-nine patients admitted to a palliative care unit receiving oral morphine (n = 19) or continuous subcutaneous (sc) morphine infusions (n = 10). Serum concentrations of morphine, M6G and M3G were obtained at the same time on four consecutive days. If readmitted, the patients were followed for another trial period. Day-to-day variations in serum concentrations and ratios were determined by estimating the percent coefficient of variation (CV = (mean/SD) x100). RESULTS: The patients' median morphine doses were 90 (range; 20-1460) mg/24 h and 135 (range; 30-440) mg/24 h during oral and sc administration, respectively. Intraindividual fluctuations of serum concentrations estimated by median coefficients of day-to-day variation were in the oral group for morphine 46%, for M6G 25% and for M3G 18%. The median coefficients of variation were lower in patients receiving continuous sc morphine infusions (morphine 10%, M6G 13%, M3G 9%). CONCLUSION: These findings indicate that serum concentrations of morphine and morphine metabolites fluctuate. The fluctuations found in our study are not explained by changes in morphine doses, administration of other drugs or by time for collection of blood samples. As expected the day-to-day variation was lower in patients receiving continuous sc morphine infusions compared with patients receiving oral morphine.

Adult↗
PubMed2003

Immediate- or sustained-release morphine for dose finding during start of morphine to cancer patients: a randomized, double-blind trial.

A titration procedure using immediate-release morphine given 4-hourly is recommended during start of oral morphine for cancer pain. This recommendation is not based on evidence from controlled studies, and many physicians start morphine treatment with controlled-release morphine. We included 40 patients with malignant disease and pain despite treatment with opioids for mild to moderate pain in a randomized, double-blind, double-dummy, parallel-group study comparing titration with immediate-release morphine given 4-hourly with titration with sustained-release morphine given once daily. The primary end point was the time needed to achieve adequate pain relief Secondary end points were other symptoms (nausea, tiredness, lack of sleep, vertigo, appetite and constipation), health related quality of life and patient satisfaction. The mean times needed for titration were 2.1 (95% CI; 1.4-2.7) days using immediate-release morphine and 1.7 (95% CI; 1.1-2.3) days using sustained-release morphine. Patients titrated with immediate-release reported statistically significant more tiredness at the end of titration. We observed no other differences in adverse effects or health related quality of life functions between the two treatments. Similar global satisfactions with the morphine treatments were reported. In conclusion, a simplified titration using sustained-release morphine once daily is equally effective as immediate-release morphine given 4-hourly.

Aged↗
PubMed2003

Routine drug monitoring of serum concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide do not predict clinical observations in cancer patients.

The clinical importance of routine drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. We measured morphine, M6G and M3G serum concentrations in cancer pain patients receiving oral (n = 263, median dose 80 mg/24 hours) or subcutaneous (sc) (n = 35, median dose 110 mg/24 hours) morphine. Regression analyses were performed to investigate if serum concentrations of morphine, M3G and M6G predicted pain intensity (Brief Pain Inventory), health-related quality-of-life variables (EORTC QLQ-C30) and cognitive function (Mini-Mental Score). Serum concentrations were also compared in patients categorized as morphine 'treatment successes' and 'treatment failures'. We observed that serum concentrations of morphine, M6G or M3G did not predict pain intensity, cognitive function, nausea or tiredness. 'Treatment failures' caused by nausea, tiredness, cognitive failure or constipation did not have statistically significant different morphine, M6G and M3G serum concentrations than patients classified as 'treatment successes'. In conclusion, this study did not observe any concentration-effect relationships of morphine, M3G or M6G with pain intensity, nausea, constipation, tiredness or cognitive failure in blood samples obtained during routine clinical drug monitoring in cancer patients. This result suggests that therapeutic drug monitoring as a routine tool during chronic morphine treatment has limited value for clinical decision making.

Administration, Oral↗
PubMed2002

Morphine glucuronide-to-morphine plasma ratios are unaffected by the UGT2B7 H268Y and UGT1A1*28 polymorphisms in cancer patients on chronic morphine therapy.

OBJECTIVE: UDP-glucuronosyltransferase (UGT) 2B7 is the major UGT isoform responsible for the 3- and 6-glucuronidation of morphine in humans. Studies in rats have indicated that UGT1A1 may also contribute to the formation of morphine 3-glucuronide (M3G). Our objective was to investigate whether the UGT2B7 H268Y and UGT1A1*28 polymorphisms contribute to the variability in morphine glucuronide-to-morphine plasma ratios among cancer patients undergoing analgesic therapy with morphine. METHODS: Seventy patients with normal hepatic and renal function using slow-release morphine to relieve cancer pain were included. UGT2B7 genotyping was performed using restriction enzyme analysis of polymerase chain reaction (PCR)-amplified DNA fragments. Wild-type and variant alleles of the UGT1A1 gene were identified using sizing of PCR-amplified fragments. Morphine 6-glucuronide (M6G)/morphine, M3G/morphine, and M3G/M6G plasma ratios were compared between genotypes. RESULTS: The M3G/morphine, M6G/morphine, and M3G/M6G plasma ratios varied 16-, 42-, and sevenfold, respectively, among individuals. No statistically significant differences in plasma ratios were found between individuals possessing UGT2B7 H/H ( n=20), H/Y ( n=30), or Y/Y ( n=20) genotypes. Five patients were homozygous for the UGT1A1 TA(7) allele, which is associated with reduced UGT1A1 gene expression. However, the mean M3G/M6G and M3G/morphine plasma ratios in TA(7) homozygous subjects did not differ significantly from those of heterozygous or homozygous wild-type (TA(6)) individuals. CONCLUSION: The UGT2B7 H268Y polymorphism cannot account for the considerable variation in glucuronide-to-morphine ratios in cancer patients. Moreover, the contribution of UGT1A1 to the formation of M3G appears to be of minor biological significance, at least in a UGT2B7 background.

Adult↗
PubMed2002

The Norwegian brief pain inventory questionnaire: translation and validation in cancer pain patients.

The European Association of Palliative Care recommends the Brief Pain Inventory questionnaire (BPI) as a pain assessment tool in clinical studies. After translation into Norwegian, we administered the BPI to 300 hospitalized cancer patients. Cronbach's alphas were computed to assess reliability, and factor analysis was utilized to ascertain construct validity. The BPI interference and pain severity scales were validated against items on pain intensity and pain influence on daily function in the European Organization for Research and Therapy of Cancer (EORTC) QLQ-C30 questionnaire. In total, 235 patients (78%) were able to complete the BPI questionnaire, but 82 (35%) of these questionnaires had one or more missing items. Cronbach's alphas were 0.87 for the pain severity and 0.92 for the interference scales. A factor analysis identified three factors; pain intensity, interference with physical function, and interference with psychological functions/sleep. These three factors explained 82% of the variance. The correlation between BPI pain severity index and the EORTC QLQ-C30 item on pain intensity was 0.70 (P < 0.001). The correlation between BPI interference index and the EORTC QLQ-C30 item on pain influence on daily living was 0.62 (P < 0.001). We conclude that BPI has satisfactory psychometric properties, but is not completed by a significant proportion of patients. Further research is needed to establish pain assessment tools for patients unable to answer a comprehensive pain questionnaire, to establish routines for analysis of missing values, and to investigate if pain interference items also reflect disease-related impairment.

Adult↗
PubMed2002

Self-reports are not related to objective assessments of cognitive function and sedation in patients with cancer pain admitted to a palliative care unit.

Cancer patients often report complaints of cognitive impairment and sedation. It is not well known if subjective complaints reflect objective assessments of cognitive function (CF) and sedation. We obtained self-reports of sedation and CF from 29 patients admitted to a palliative care unit and receiving morphine treatment. Sedation was reported on a verbal rating scale (VRS) and CF was reported using the EORTC QLQ-C30 health-related quality-of-life questionnaire CF scale. The self-reports were compared with objective assessments of sedation and CF by applying the Observer's Assessment of Alertness/Sedation (OAA/S) scale and Mini Mental State Examination (MMS), respectively. The assessments were repeated for seven patients who were readmitted to the palliative care unit. The patient self-reports of memory, concentration and sedation were dichotomized into noncomplainers and complainers. The percentages of complainers were 54%, 46% and 37% for memory, concentration and sedation, respectively. Patients who complained from difficulties with concentration or memory did not score differently from noncomplainers on objective assessments of CF (MMS score), but had a significantly higher level of fatigue. Patients complaining from sedation did not score differently from noncomplainers on objective assessments of sedation (OAA/S score). We observed no significant correlations between EORTC QLQ-C30 CF scale scores and MMS scores, or between VRS sedation scores and OAA/S scores. The study demonstrates a lack of relationship between patient self-reports and objective methods for assessing sedation and cognitive failure. This finding illustrates the importance of differentiating between observations and patient self-reports. The results also question the validity of patient self-reports for measurements of cognitive failure and sedation.

Adult↗