Biomedical subjects

C Mignat

Publications and source records attributed to C Mignat.

10 recordsLinked to original sources

PubMed1998

Determination of pravastatin in human plasma by high-performance liquid chromatography with ultraviolet detection.

A sensitive high-performance liquid chromatographic (HPLC) method for the quantitation of the HMG-CoA reductase inhibitor pravastatin in human plasma is described. Sample preparation based on reversed-phase solid-phase extraction using triamcinolone acetonide as internal standard (I.S.). The compounds were separated on C18 reversed-phase analytical column and then determined by ultraviolet detection. The recovery of pravastatin from plasma was 69.2+/-6.7% (mean+/-S.D.). The limit of detection for pravastatin in aqueous solution was 0.4 ng, the limit of quantitation in plasma was 2 ng/ml. In a preliminary pharmacokinetic study with two healthy volunteers the t1/2 of pravastatin in plasma was found to be 0.8 and 2.3 h.

Chromatography, High Pressure Liquid↗

PubMed1998

Does prolonged oral treatment with sustained-release morphine tablets influence immune function?

UNLABELLED: Opioids such as morphine are the mainstay of acute and chronic pain treatment. The purpose of this study was to investigate the immunosuppressive effects of morphine in patients with pain syndromes. We investigated 10 patients with chronic pain syndromes undergoing treatment with oral sustained-release morphine (30-240 mg/d) before and after 1,4, and 12 wk of treatment compared with healthy control subjects without morphine treatment. Immunological variables of the cellular and humoral immune axis showed that 1) total lymphocyte counts and the distribution of lymphocyte subpopulations, including helper T-cell/suppressor cytotoxic T-cell ratios (CD4/CD8 ratios), did not change compared with baseline or healthy control subjects; 2) proliferation of peripheral mononuclear cells (PMC) was not impaired by morphine treatment; 3) interleukin 2 production increased after 4 wk of treatment with morphine; and 4) immunoglobulin (Ig) production was reduced before initiation of therapy in pain patients and decreased further during morphine treatment, whereas Ig concentrations in the circulation remained at normal levels. These results indicate that treatment with oral, sustained-release morphine does not have a suppressive effect on overall PMC function. On the other hand, Ig production was impaired in patients with chronic pain and was further suppressed by morphine. Whether this suppression of humoral immune function has a clinical impact on the immune system as a whole remains to be determined. IMPLICATIONS: Treatment of patients with chronic pain with oral, sustained-release morphine does not influence cellular immune function, but it suppresses the already attenuated production of immunoglobulins.

Administration, Oral↗

PubMed1997

Clinically significant drug interactions with new immunosuppressive agents.

Tacrolimus (FK506), mycophenolate mofetil, sirolimus (rapamycin), gusperimus, and monoclonal antibody preparations are new immunosuppressive agents, some of which are already approved for clinical use, while others are currently undergoing clinical trials. The present article provides an overview of adverse drug interactions between these immunosuppressants and other drugs which may be used concomitantly. Preliminary data suggest that a pharmacodynamic interaction can occur between tacrolimus and nonsteroidal anti-inflammatory drugs, associated with an increased risk of nephrotoxicity. Erythromycin, clarithromycin, clotrimazole, fluconazole, ketoconazole, and danazol have been shown to increase tacrolimus blood concentrations, while rifampicin (rifampicin) was found to decrease tacrolimus blood concentrations. Evidence from experimental studies suggest that several other drugs also known to affect cytochrome P450 activity may have significant effects on the pharmacokinetics of tacrolimus. On the other hand, tacrolimus itself may inhibit the metabolism of coadministered drugs. This interaction may be attributed to the enhanced renal impairment which has been observed in patients treated with tacrolimus and cyclosporin. The bioavailability of mycophenolic acid, the active metabolite of mycophenolate mofetil, has been reported to be reduced by aluminium/magnesium hydroxide-containing antacids and cholestyramine. Mycophenolic acid, sirolimus and gusperimus may impair bone marrow function and this adverse effect may be enhanced by concomitant administration of other myelosuppressive drugs. There is some evidence that coadministered sirolimus and cyclosporin cause an increase in each other's blood concentrations. An increased risk of central nervous system adverse effects has been described following the combined use of indomethacin and the monoclonal antibody muromonab CD3 (OKT3).

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1996

[Morphine].

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Analgesics, Opioid↗

PubMed1996

Synthesis, opioid receptor affinity, and enzymatic hydrolysis of sterically hindered morphine 3-esters.

With the intention of preparing prodrugs, 10 morphine 3-esters were synthesized and evaluated in vitro for opioid receptor binding and enzymatic hydrolysis. The results of binding assays performed on homogenates of guinea pig brain demonstrate a loss in affinity of morphine to mu-, delta-, and kappa-receptors by esterification at the 3-position. The conversion of the esters to morphine was determined in human plasma by HPLC analysis. The half-lives of hydrolysis ranged from 0.5 to > 300 h. The investigations indicate that esterification at the 3-position results in morphine prodrugs with variable hydrolytic stability. Sterically hindered morphine 3-esters may be a promising approach to manipulate the rate of release of morphine.

Animals↗

PubMed1996

Phytohemagglutinin-dependent T-cell proliferation is not impaired by morphine.

Opioids have been reported in the literature to have immunosuppressive properties. Thus, we investigated the influence of morphine, morphine-3-glucuronide and morphine-6-glucuronide in vitro on phytohemagglutinin-stimulated proliferation of peripheral mononuclear cells from healthy humans. Furthermore, the effects of a 1-week treatment with morphine in a range of 30-240 mg/day on proliferation of lymphocytes from patients with chronic pain syndromes were evaluated. In addition, human peripheral mononuclear cell membranes were tested for specific opioid radioligand binding. The results show that i) morphine and its main metabolites do not influence mitogen-induced T-cell proliferation, ii) treatment of patients with sustained release morphine for 1 week did not impair the lymphocyte proliferative response, and iii) no specific binding of mu-, delta- and kappa-radioligands could be demonstrated to membranes of peripheral lymphocytes obtained from healthy humans. These results do not indicate an impairment of phytohemagglutinin-induced T-cell proliferation during pain treatment with sustained release morphine.

Analgesics, Opioid↗

PubMed1995

Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes.

The affinity of morphine, codeine, dihydrocodeine and their glucuronides for mu-, delta-, and kappa-opioid receptors was investigated. Binding was studied on guinea-pig brain homogenates with [3H]DAMGO, [3H]DPDPE, and [3H]U69593. The substitution of the free phenolic group of morphine caused a decrease in binding at opioid receptors without affecting the mu/delta-ratio nor that of mu/kappa. Glucuronidation of the 6-hydroxyl group of morphine, codeine or dihydrocodeine did not affect the affinity to mu-receptors, slightly increased the affinity for delta-receptors and reduced the affinity for kappa-receptors. The 6-glucuronides possess a decreased selectivity for mu-receptors over delta-receptors whereas that for mu- over kappa-receptors was increased. It is concluded that chemical variations at 3- and 6-position of morphine independently affect the affinity to opioid receptor subtypes.

Animals↗

PubMed1995

Plasma and cerebrospinal fluid concentrations of morphine and morphine glucuronides in rabbits receiving single and repeated doses of morphine.

The pharmacokinetics of morphine in plasma and the distribution of morphine and its glucuronidated metabolites within the cerebrospinal fluid were investigated in rabbits. After single morphine dosage, the plasma AUC ratio of morphine-3- glucuronide/morphine was 11.1 compared with 0.14 for morphine-6-glucuronide/morphine. The similar elimination half-lives of morphine (107 min), morphine-3-glucuronide (122 min), and morphine-6-glucuronide (105 min) suggested the glucuronidation to be the rate-limiting step, which was substantiated by the observation that morphine-3-glucuronide becomes eliminated four times faster when applied intravenously. Both after single and repeated morphine administration, the ratios of CSF and plasma levels of the parent drug were higher than those of morphine-3-glucuronide or morphine-6-glucuronide. These data demonstrate a poor penetration of the glucuronides across the blood-brain barrier and do not support the previously postulated accumulation of morphine-6-glucuronide in the central nervous system during chronic morphine treatment.

Animals↗

PubMed1995

ACE inhibitors. Drug interactions of clinical significance.

ACE inhibitors are used widely in the treatment of hypertension and congestive heart failure, but there is only limited information on adverse interactions between ACE inhibitors and other cardiovascular or noncardiovascular drugs. The present article provides an overview of this issue, with emphasis on those interactions having the greatest clinical implications. In patients who have been sodium and/or volume depleted by thiazide or loop diuretics, the additional use of ACE inhibitors can lead to an excessive reduction in blood pressure and symptomatic hypotension. An increase in serum potassium levels may occur after coadministration of potassium-sparing diuretics and ACE inhibitors, resulting in hyperkalaemia especially in patients with renal insufficiency. The incidence of acute renal failure may be associated with ACE inhibitor therapy when these drugs are combined with nonsteroidal anti-inflammatory agents and given to patients whose renal function becomes increasingly dependent on angiotensin II and prostaglandins. There is some evidence, albeit scant, linking ACE inhibitors with the induction of lithium toxicity in patients maintained on lithium, and with the occurrence of severe hypersensitivity reactions in patients undergoing haemodialysis, venom immunisation or concomitant allopurinol therapy.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1994

The stability of mixtures of morphine hydrochloride, bupivacaine hydrochloride, and clonidine hydrochloride in portable pump reservoirs for the management of chronic pain syndromes.

The physical and chemical stability of a combination of drugs commonly administered into the epidural or intrathecal space for the treatment of chronic pain was investigated. The concentrations of bupivacaine hydrochloride, morphine hydrochloride, and clonidine hydrochloride were measured using high performance liquid chromatography. The solutions were stored in reservoir bags for up to 90 days. No macroscopic or microbiological signs of precipitation, change in color, or contamination were observed, and pH remained stable. None of the three drugs declined in concentration during the observation period. A small increase in concentration of all three drugs did occur over time, most probably due to evaporation processes. In conclusion, no problems in physical or chemical stability are to be expected when combining morphine, bupivacaine, and/or clonidine for long-term epidural or intrathecal administration. In the case of clinically apparent loss of analgesic efficacy, other mechanisms should be considered.

Bupivacaine↗