Biomedical subjects

P Devillier

Publications and source records attributed to P Devillier.

At least 19 recordsLinked to original sources

PubMed1999

Leukotrienes, leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma: an update. Part I: synthesis, receptors and role of leukotrienes in asthma.

Asthma is a chronic inflammatory disease associated with airflow obstruction. Airflow obstruction results from contraction of airway smooth muscle, mucosal oedema, increased secretion of mucus and infiltration of the airway wall by inflammatory cells, particularly eosinophils. Leukotrienes are thought to contribute to the pathophysiology of asthma. Leukotrienes are synthesised from arachidonic acid by a specific synthesis pathway whose key enzyme is 5-lipoxygenase. Cysteinyl leukotrienes (leukotrienes C4, D4 and E4) have been shown to mimic all the pathologic changes that are characteristic of asthma, whereas leukotriene B4 does not appear to exert biological properties relevant to asthma. Cysteinyl leukotrienes bind to two receptor subtypes: CysLT1 and CysLT2. Most of the biological properties of cysteinyl leukotrienes relevant to asthma are mediated through CysLT1 receptor stimulation.

Anti-Asthmatic Agents↗

PubMed1999

Leukotrienes, leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma: an update. Part II: clinical studies with leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma.

The demonstration that leukotrienes, mainly cysteinyl leukotrienes, have biological properties relevant to the pathogenesis of asthma has stimulated the development of many therapeutic compounds to block these deleterious effects. Two main classes of leukotriene modulators have been developed: CysLT1 receptor antagonists and leukotriene synthesis inhibitors. This article reviews the pharmacodynamics, the effects on baseline airway function, the protective effects in airway challenges as well as the results in chronic asthma of the different leukotriene modulators. In addition, the complementary anti-inflammatory effect of leukotriene modulators to that of corticosteroids and H1-histamine receptor antagonists is reviewed. Finally, a concise overview of the clinical responsiveness to this new class of drug, the safety and the drug interactions as well as the place in the strategies of treatment for asthmatic patients of the leukotriene modulators is also provided.

Anti-Asthmatic Agents↗

PubMed1999

Effects of amifostine on perfused isolated rat heart and on acute doxorubicin-induced cardiotoxicity.

PURPOSE: To determine the effects of amifostine on an isolated perfused rat-heart model and its protective activity with regard to cardiotoxic doxorubicin perfusion. METHODS: Langendorff constant-pressure isolated rat-heart preparations were used to analyze the effects of the drugs during a 40-min period of perfusion after a 20-min stabilization interval. The first study was conducted with amifostine alone (controls and 10(-6), 10(-5), and 10(-4) M amifostine; n=6 in each group). The second study was conducted with amifostine and doxorubicin (controls, 2.5 x 10(-5) M doxorubicin, 2.5 x 10(-5) M doxorubicin and 10(-5) M amifostine, and 2.5 x 10(-5) M doxorubicin and 10(-4) M amifostine; n=4 in each group). RESULTS: Amifostine had no significant effect on hemodynamic parameters at 10(-6), 10(-5), and 10(-4) M concentrations. However. amifostine increased the coronary flow expressed as a percentage+/-SEM of the baseline flow as follows: 82+/-4% for controls, 95+/-6% for 10(-6) M amifostine, (P=0.13), 111+/-4% for 10(-5) M amifostine (P < 0.01), and 104+/-3% for 10(-6) M amifostine (P < 0.01). When we commenced an amifostine perfusion 20 min in advance of and then during a 40-min perfusion with doxorubicin, at a cardiotoxic concentration of 2.5 x 10(-5) M the left ventricular pressures (LVDP, expressed as percentages +/-SEM of the baseline LVDP before doxorubicin) were 55+/-3% for the doxorubicin controls, 68+/-2% for doxorubicin with 10(-5) M amifostine (P=0.05), and 80+/-3% for doxorubicin with 10(-4) M amifostine (P < 0.01). Whether this protective effect might be related to the known free-radical-scavenging activity of amifostine remains to be determined. CONCLUSION: On a Langendorff-type model of rat heart, 10(-5) and 10(-4) M amifostine alone induced a coronary dilation and, when associated with a cardiotoxic concentration of 2.5 x 10(-5) M doxorubicin, 10(-5) and 10(-4) M amifostine displayed a cardioprotective effect.

Amifostine↗

PubMed1999

New calcium antagonists: synthesis, X-ray analysis, and smooth muscle relaxing effect of 3-[O-(benzyl-substituted)-oximino-ethers]-hexahydroazepin-2,3- diones.

A series of new Z and E 3-[O-(benzyl-substituted)-oximino-ether]-hexahydroazepin-2,3 -diones was prepared from the corresponding hexahydroazepin-2,3-diones and examined as smooth muscle relaxants. E and Z structures were assigned by NMR analysis and confirmed for 16 (E and Z) by an X-ray diffraction using synchrotron radiations. The nitrobenzyl derivative 16 was the most potent in vitro as relaxant of rat trachea precontracted with acetylcholine. The E isomer 16b was more potent than the Z isomer 16a. E isomer 16b is more potent than aminophylline to relax both rat trachea and human bronchus. This derivative acts mainly by inhibiting cellular influx of extracellular calcium since it inhibits potently and dose-dependently the contractions of rat trachea to high concentrations of KCI and to CaCl2 in a depolarizing medium. It appears to act weakly by inducing cGMP and cAMP synthesis. Moreover, its relaxing activity is not related to an inhibition of phosphodiesterases, to opening of potassium channels or to induction of prostaglandin synthesis. Therefore, 16b appears to work mainly as a potent calcium antagonist.

Animals↗

PubMed1999

Functional assessment of rat aorta after cold storage in different media.

Cold storage is frequently used to store isolated blood vessels for a limited period of time. However preservation of vascular smooth muscle and endothelial functions is time and medium-dependent. The present study was designed to compare the reactivity of rat aorta before and after cold storage for 24 and 48 h in one of four different solutions consisting of Hepes-buffered Krebs solution, Belzer solution, Krebs solution, and Eurocollins solution. Smooth muscle and endothelial functions of the rat aorta were assessed using in vitro isometric tension measurement. The results obtained for vessels preserved for 24 and 48 h were compared with those for vessels studied immediately after harvesting. Sensitivity and maximum contraction to KCl and norepinephrine were not altered in rat aorta preserved up to 48 h in Hepes-Krebs and Belzer solutions. In contrast, the amplitude of contraction elicited by KCl was significantly reduced by 50% and 77% in aorta stored for 24 and 48 h in Krebs solution and by 77% and 96% in those stored in Eurocollins solutions. Similarly, the maximal contraction elicited by norepinephrine was significantly reduced by 60% and 45% in arteries stored for 24 and 48 h in Krebs solution and by 34% and 86% in those stored in Eurocollins solution. In contrast, cold storage in the different media did not alter the relaxations elicited by sodium nitroprusside and forskolin. The endothelium-dependent relaxations in response to acetylcholine were not statistically modified after preservation up to 48 h in Hepes-Krebs solution. In contrast, the maximal relaxations to acetylcholine were significantly decreased after storage for 24 and 48 h in Belzer, Krebs and Eurocollins solutions. These results suggest that among the four media studied, Hepes-Krebs solution is the most suitable medium for the storage of blood vessels under hypothermic conditions.

Animals↗

PubMed1998

Predominant role of the Fab fragment in delaying hyperacute rejection in guinea pig-to-rat xenotransplantation.

BACKGROUND: Human intravenous immunoglobulin G delayed xenogeneic hyperacute rejection (HAR) in the guinea pig-to-rat combination. We investigated the respective roles of the Fc and Fab fragments of the IgG molecule in this inhibitory effect. METHODS: By using a guinea pig-to-rat heart transplantation model, the efficiency of IgG, Fab, and Fc in prolonging the grafted heart's survival time (ST) was compared. RESULTS: A dose-dependent increase in the ST was observed with Fab (r=0.74, P < 0.0001), IgG (r=0.57, P < 0.001), and Fc (r=0.51, P < 0.01). The linear regression slopes with Fab and with IgG were, respectively, sevenfold and fourfold steeper than with Fc. The ST was significantly longer than controls (23+/-7 min) after infusion of 2 g/kg IgG (147+/-42 min) or 1 g/kg Fab (176+/-38 min), whereas the highest dose of Fc (1.5 g/kg) did not induce significant prolongation of ST. In terms of equivalent functional doses, 1 g/kg Fab was significantly more potent in prolonging the ST than 1.5 g/kg IgG (87+/-25 min) or 0.5 g/kg Fc (33+/-14 min). Analysis of the rejected hearts evidenced edema, necrosis, and rat C3 deposits characteristic of HAR. CONCLUSION: These results indicated that the delaying action of intravenous immunoglobulin G on HAR in the guinea pig-to-rat combination is mostly mediated through the Fab fragment.

Animals↗

PubMed1998

Glibenclamide inhibits thromboxane A2-induced contraction in human internal mammary artery and saphenous vein.

Glibenclamide, like other hypoglycemic sulfonylurea derivatives, is a potent blocker of ATP-regulated K+ channels. In addition, it is reported to inhibit prostanoid-induced contractions of isolated vascular smooth muscle from different animal species. We investigated the effect of glibenclamide on the thromboxane A2-mimetic U-46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy-prostaglandin F2alpha)-induced contractions in human isolated internal mammary arteries and saphenous veins. In the two vascular preparations, glibenclamide (3, 10 and 30 microM) caused a concentration-dependent shift to the right of the U-46619 contraction-response curve with a reduction, at the highest concentrations, in the maximal responses. This inhibitory effect appears selective for thromboxane A2-induced contractions since glibenclamide (30 microM) did not alter the contraction of internal mammary arteries in response to norepinephrine and of saphenous veins in response to 5-hydroxytryptamine (5-HT) and endothelin-1. However, glibenclamide reduced the endothelin-1-induced contraction in internal mammary arteries. The endothelin-1-induced contractions were similarly inhibited by GR 32191 ([1R-[1alpha(Z),2beta,3beta,5alpha]]-(+)-7-[5-([1,1'-b iphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-++ +heptonoic acid, a thromboxane A2 receptor antagonist. These results suggest that glibenclamide also reduced the endothelin-1-induced contractions by inhibiting a thromboxane A2 receptor-mediated component of the contraction elicited by this peptide. In conclusion, glibenclamide clearly appears to exert a specific inhibitory influence on prostanoid-induced contractions in human internal mammary arteries and saphenous veins.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1998

Inhibitory effects of large Ca2+-activated K+ channel blockers on beta-adrenergic- and NO-donor-mediated relaxations of human and guinea-pig airway smooth muscles.

In human bronchi, relaxations to salbutamol and sodium nitroprusside were performed in the presence or absence of blockers of the large Ca2+-activated K+-channels (BKCa): charybdotoxin (Chtx), iberiotoxin (Ibtx) or tetraethylammonium (TEA). In bronchi under basal tone in presence of indomethacin (1 microM) or precontracted with acetylcholine (in presence or absence of indomethacin), the relaxations to salbutamol or sodium nitroprusside were unaffected or weakly inhibited by pretreatment with the BKca blockers (Chtx (100 nM), Ibtx (100 and 300 nM) and TEA (1 mM)). Significant inhibitions were mainly observed with TEA (1 mM) and iberiotoxin at high concentration (300 nM). These results contrasts with the potent inhibitory effects exerted by Chtx (100 nM) or Ibtx (100 nM) in guinea-pig trachea precontracted with acetylcholine in absence or presence of indomethacin indicating that human airways are less susceptible to BKCa blockade than guinea-pig airways. In addition, the BKCa blockers induced slowly developing contractions of human bronchi at basal tone. The contraction induced by TEA (1 mM) was abolished by verapamil (10 microM) suggesting that BKca blockade promotes an increase in membrane Ca2+-conductance through activation of voltage-gated Ca2+-channels. Verapamil also reversed the effects of TEA on salbutamol-induced relaxations in human bronchi as well as the effects of Ibtx on salbutamol- or sodium nitroprusside-induced relaxations in guinea-pig trachea. These data suggest that BKCa blockers induce activation of voltage-gated Ca2+-channels and therefore influx of Ca2+ which in turn cause a functional antagonism of beta2-adrenoceptor-agonist- and NO-donor-induced relaxations. Moreover, the BKCa opener, NS-1619, induced weak relaxations in human bronchi and guinea-pig trachea which were not blocked by TEA or Ibtx suggesting that BKCa opening is of minor significance for the relaxation of human airway smooth muscles. In conclusion, although a wealth of studies have demonstrated that beta-adrenoceptor agonists or NO-donors activate BKCa, the present study provides evidence that in human bronchi, as recently suggested in guinea-pig trachea, opening of BKCa does not appear to functionally participate in the relaxation to these relaxant agents.

Adrenergic beta-Agonists↗

PubMed1998

Functional assessment of human femoral arteries after cryopreservation.

PURPOSE: An established method of cryostorage that might preserve the vascular and endothelial responses of human femoral arteries (HFAs) to be transplanted as allografts was studied. METHODS: HFAs were harvested from multiorgan donors and stored at 4 degrees C in Belzer solution before cryostorage. One hundred eleven HFA rings were isolated and randomly assigned to 1 control group of unfrozen HFAs and 2 groups of HFAs cryopreserved for 7 and 30 days, respectively. Cryopreservation was performed in Elohes solution containing dimethyl sulfoxide (1.8 mmol/L), and the rate of cooling was 1.6 degrees C/min, until -141 degrees C was reached. The contractile and relaxant responses of unfrozen and frozen/thawed arteries were assessed in organ bath by measurement of isometric force generated by the HFAs. RESULTS: After thawing, the maximal contractile responses to all the contracting agonists tested (KCl, U46619 [a thromboxane A2-mimetic], norepinephrine, serotonin, and endothelin-1) were in the range of 7% to 34% of the responses in unfrozen HFAs. The endothelium-independent relaxant responses to forskolin and verapamil were weakly altered, whereas the endothelium-independent relaxant responses to sodium nitroprusside were markedly reduced. Cryostorage of HFAs also resulted in a loss of the endothelium-dependent relaxant response to acetylcholine. The vascular and endothelial responses were similarly altered in the HFAs cryopreserved for 7 and 30 days. CONCLUSION: The cryopreservation method used provided a limited preservation of HFAs contractility, a good preservation of the endothelium-independent relaxant responses, but no apparent preservation of the endothelium-dependent relaxation. It is possible that further refinements of the cryopreservation protocol, such as a slower rate of cooling and a more controlled stepwise addition of dimethyl sulfoxide, might allow better post-thaw functional recovery of HFAs.

Cryopreservation↗

PubMed1998

Frusemide inhibits angiotensin II-induced contraction on human vascular smooth muscle.

AIMS: Frusemide is widely used in the treatment of acute pulmonary oedema, chronic congestive heart failure and, to a lesser degree, in the treatment of hypertension. Evidence suggests that frusenuide exerts an anti-vasoconstrictor effect independent of its diuretic properties. Since angiotensin II is a highly potent vasoconstrictor involved in the pathophysiology of these diseases, we have investigated the effect of frusemide on the contraction elicited by angiotensin II on human internal mammary artery (IMA) and saphenous vein (SV). METHODS: Rings of IMA and SV were suspended for isometric tension recording in organ baths. Concentration-response curves to angiotensin II were performed in the absence (control) or in the presence of frusemide (10(-6) to 10(-3) M). In addition, the effect of frusemide was evaluated after cyclooxygenase inhibition by indomethacin (10(-6) M) and was compared with those of the other loop diuretic bumetanide (10(-4) M). RESULTS: Frusemide induced a concentration-dependent decrease of the contraction elicited by angiotensin II on IMA and SV. On both vessels, the inhibitory effect on the maximal contraction to angiotensin II was significant with concentrations of frusemide from 10(-5) to 10(-3) M. Angiotensin II potency (pD2) was only reduced by 10(-3) M frusemide. The effect of frusemide was not altered in the presence of indomethacin. Bumetanide was less potent than frusemide in inhibiting angiotensin II-induced contractions in both IMA and SV. CONCLUSIONS: Frusemide, at concentrations in the therapeutic range (10(-5) M), inhibits angiotensin II-induced contraction on human isolated IMA and SV. This inhibitory effect is cyclooxygenase independent and appears mediated, at least in part, by inhibition of Na+/K+/2Cl- symport. Reduction in the vasoconstrictor effect of angiotensin 1 may be involved in the therapeutic efficacy of frusemide.

Angiotensin II↗

PubMed1998

In vitro-induced human airway hyperresponsiveness to bradykinin.

Lipopolysaccharide (LPS) and interleukin (IL)-1beta have been reported to induce airway hyperresponsiveness in several animal models. This study investigated the effect of LPS or IL-1beta on bradykinin-induced human isolated bronchi contraction. LPS (100 ng x mL(-1) for 3-6 h) and IL-1beta (3x10(-10) and 3x10(-9) M for 20 min to 3 h) time-dependently potentiated bradykinin-induced contraction. This contraction was abolished, as in control experiments, by indomethacin (10(-6) M) or by the thromboxane (Tx) receptor antagonist GR 32191 but not by the cyclo-oxygenase-2 inhibitor, CGP28238. In contrast, the Tx mimetic U46619-induced contraction of human bronchi was not enhanced IL-1beta pretreatment. In the presence of GR 32191 (10(-6) M), bradykinin induced a prostanoid dependent relaxation that was not significantly modified by IL-1beta pretreatment. Determination of prostanoids in the organ bath fluid showed that bradykinin induced TxB2, the stable metabolite of TxA2, and 6-keto prostaglandin F1alpha, the stable metabolite of PGI2, release. Only TxA2 release was potentiated by IL-1beta. Taken together our results suggest that interleukin-1beta (1-3 h)-induced potentiation of the effect of bradykinin is linked to an increased activity of thromboxane synthase and, in turn, to increased thromboxane synthesis.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1998

[Beta-2 agonists].

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Adrenergic beta-Agonists↗

PubMed1997

Effect of low-dose positive inotropic drugs on human internal mammary artery flow.

BACKGROUND: Dobutamine (a beta-receptor agonist), enoximone (a type III selective phosphodiesterase inhibitor), and epinephrine (an alpha- and beta-mimetic) frequently are used in the perioperative management of patients undergoing coronary artery bypass grafting. METHODS: We performed a double-blind clinical study to compare the effects on internal mammary artery free flow of low doses of these three positive inotropic drugs. Thirty patients in whom the left internal mammary artery was used for coronary artery bypass grafting were randomized into three groups. Internal mammary artery free flow and hemodynamic measurements were evaluated before and 10 minutes after the intravenous infusion of dobutamine (3 microg x kg(-1) x min(-1)), enoximone (200 microg/kg), or epinephrine (0.05 microg x kg(-1) x min(-1)). RESULTS: A significant increase in free flow occurred only in the dobutamine group (33 +/- 7.5 and 42.2 +/- 7.9 mL/min before and after drug infusion, respectively; p = 0.013). Comparison of the increase in flow between the groups, however, showed no difference. These drugs, at doses designed to produce a positive inotropic effect, caused little increase in the free flow of the internal mammary artery. CONCLUSIONS: The use of dobutamine, enoximone, and epinephrine as low-dose positive inotropic treatments in the perioperative and postoperative periods of coronary artery bypass grafting should depend on their positive inotropic effects rather than their vasodilative effects on the arterial grafts.

Adrenergic beta-Agonists↗

PubMed1997

Thromboxane A2 and related prostaglandins in airways.

Asthma is now thought to be a chronic inflammatory disease of the airways. The roles of prostanoids, thromboxane A2 (TXA2) and the prostaglandins (PGs) in the pathogenesis and pathophysiology of asthma have fostered a wealth of studies but remain controversial. TXA2 and the bronchoconstrictor PGs, PGD2 and PGF2 alpha, are generated in greater amounts in asthmatic than in normal subjects. TXA2 is a potent constrictor of airway smooth muscle, an inducer of acetylcholine release and of airway microvascular leakage. It may participate in the thickening and the remodeling of the airway wall which may contribute to the airway hyperresponsiveness, a typical feature of asthma. Strategies for inhibition of TXA2 effects include antagonism of the TXA2 receptor (TP receptor) and inhibition of the thromboxane synthase. TP receptor antagonists could block the effects of all the bronchoconstrictor prostanoids because TXA2 as well as the bronchoconstrictor PGs act through activation of lung TP receptor. The recent development of specific and potent TP receptor antagonists and inhibitors of thromboxane synthase has provided tools to assess the role of TXA2 and broncho-constrictor PGs in the pathophysiology of asthma.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1997

Pharmacokinetics of intrarectal nalbuphine in children undergoing general anaesthesia.

The pharmacokinetics of nalbuphine (0.3 mg/kg) administered by the rectal route were studied in ten children undergoing general anaesthesia for minor surgery. Blood sampling was carried out for 8 h after rectal administration and plasma drug concentrations were measured by high performance liquid chromatography using electrochemical detection after an optimized solid-phase extraction procedure. The mean time to achieve the maximum plasma concentration (Cmax = 24 +/- 15 ng/mL) was 25 +/- 11 min and the elimination half-life was 2.7 +/- 0.7 h. The coefficients of variation for Cmax and the concentration-time curve (AUC) were 62 and 68%, respectively. Although rectal absorption is considered irregular, the large intersubject variability is also explainable by a variable hepatic bypass for a drug, like nalbuphine, that undergoes extensive first-pass metabolism. No problem of analgesic efficacy or of local tolerance was reported. In conclusion, the rectal route of administration provides a rapid and reliable absorption of nalbuphine.

Administration, Rectal↗

PubMed1997

[Leukotriene antagonists: a new approach in the treatment of asthma].

Inflammation plays an essential role in the genesis of airflow obstruction and bronchial hyper-reactivity in the early stages of clinical asthma. The treatment of bronchial inflammation has become an essential element in the therapeutic strategy and principally rests on inhaled glucocorticoids. Amongst a number of inflammatory mediators leukotrienes occupy a privileged place by the power of their inflammatory and constrictor effects on bronchial smooth muscles. These properties have justified the clinical development of inhibitors of their synthesis and of specific antagonists to their receptors. Leukotriene antagonists are specific for a sub type of leukotriene receptors C4, D4 and E4 which is implicated in the majority of the bronchial constrictor and inflammatory effects of leukotrienes. The antagonists of Cys-LT1 receptor but also the inhibitors of the leukotriene synthesis exert an additive bronchodilator effect to those of B2 stimulants confirming an efficacious protection vis a vis bronchial provocation tests and above all they improve the clinical scores, lung function and also enable a decrease in the consumption of beta 2 agonists. The marketing of these products represents a major event because it corresponds to the advent of a new therapeutic class. The ease of administration by the oral route, their demonstrated efficacy and their good tolerance profile (in particular for ICI 204.219, and antagonists to Cys-LT1 receptors) are elements which foresee a success for this new asthmatic treatment. However numerous studies, notably comparative studies vis a vis reference treatments will be necessary to define their place in the strategic approach to the treatment of asthma.

Anti-Asthmatic Agents↗

PubMed1997

[The anti-leukotrienes: their use in asthma].

Inflammation in asthma plays a predominant role in the genesis of bronchial obstruction and hyperreactivity. Treatment of bronchial inflammation since the early stages of asthma has become an essential element of therapeutic strategy and rests chiefly on inhaled glucocorticoids. However, inhaled glucocorticoids pose some problems in terms of inhalation technique, compliance, local tolerance and, to a lesser extent and at high doses, of systemic tolerance. Antileukotrienes represent a new class of potential anti-asthma drugs. They act either by inhibition of 5-lipoxygenase, a key enzyme in the leukotriene (LT) synthesis pathway, or by blocking LT receptors. The LT antagonists developed in asthma are mainly specific for a receptor subtype, the CysLT1 receptor, involved in the bronchoconstrictor and inflammatory effects of sulfidopeptide leukotrienes (LTC4, D4 and E4). Two antagonists of CysLT1 receptors have been recently launched on the market: ONO-1078, pranlukast, Onon and ICI-204,219, zafirlukast, Accolate. The CysLT1 antagonists cause bronchodilatation with a beta 2-agonist additive effect, confer effective protection in bronchial provocation studies and particularly, they improve clinical scores, pulmonary function and beta 2-agonist rescue inhaler use. Additional studies, especially comparative with respect to reference treatments, mainly inhaled glucocorticoids, will be required to define their place in the global strategy for asthma management.

Anti-Asthmatic Agents↗

PubMed1996

Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the neonate.

Nalbuphine, a mixed agonist-antagonist opiate, is commonly used as a systemic analgesic during labour. Recent reports of perinatal adverse effects prompted us to carry out therapeutic nalbuphine monitoring in obstetric analgesia. Because data on fetomaternal transfer are scarce and the pharmacokinetics of this drug in the neonate are largely unknown, we report data obtained from 28 parturients treated with nalbuphine either intramuscularly and/or intravenously during labour. Plasma nalbuphine levels were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. At delivery, 30-150 min after maternal administration, nalbuphine concentrations ranged from 5.0 to 79.2 ng.ml-1 in mother plasma samples and from 3.0 to 46.6 ng.ml-1 in umbilical cord plasma samples. Nalbuphine concentrations were highly correlated to dose. The fetomaternal ratio was high: 0.74 and not correlated to the administered dose of nalbuphine. An estimated plasma half-life of 4.1 h was calculated from two determinations in the neonate based on the assumption of a monoexponential decay of nalbuphine concentrations. Apart from a flattening of the fetal heart rate tracing in 54% of the cases, only one neonate had a low Apgar score at birth. The apparent prolonged half-life of nalbuphine in the neonate indicates the usefulness of an intramuscular injection of naloxone to prevent recurrence of cardiorespiratory depression due to nalbuphine administration to the mother.

Adult↗