Gleiter, Christoph H.

[["dc.bibliographiccitation.firstpage","838"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Pflügers Archiv - European Journal of Physiology"],["dc.bibliographiccitation.lastpage","844"],["dc.bibliographiccitation.volume","439"],["dc.contributor.author","Freudenthaler, S. M."],["dc.contributor.author","Lucht, I."],["dc.contributor.author","Schenk, T."],["dc.contributor.author","Brink, M."],["dc.contributor.author","Gleiter, Christoph H."],["dc.date.accessioned","2018-11-07T08:29:09Z"],["dc.date.available","2018-11-07T08:29:09Z"],["dc.date.issued","2000"],["dc.description.abstract","Current evidence suggests that angiotensin II may be involved in the regulation of renal erythropoietin (EPO) production. The present study assessed the role of angiotensin II (A II) in different doses in the control of EPO production in humans. In a parallel, randomized, placebo-controlled open design, 60 healthy male volunteers received a 6-h intravenous infusion of: placebo (placebo, electrolyte solution), a presser dose of A II (1-3 mu g/min; A II press), a combination of a presser dose of A II and the selective AT(1)-receptor blocker losartan, 50 mg (A II press + L), a subpressor dose of A II (0.0375-0.15 mu g/min; A II subpress) and a combination of a subpressor dose of A II and losartan (A II subpress + L). A II press treatment resulted in a significant increase of the maximum EPO concentration (C-maxEPO, 41% higher versus placebo) and the amount of EPO produced in 24 h (AUC(EPO(0-24 h)), 61% larger versus placebo), A II subpress treatment increased C-maxEPO (35% higher versus placebo) and AUC(EPO(0-24 h)) (34% larger versus placebo). A II press + L and A II subpress + L treatments did not significantly increase C-maxEPO and AUC(EPO(0-24 h)) compared to placebo. A II affects EPO production in a dose-dependent manner. The signal seems to be mediated via ATI-receptors. A II appears to be one modulator EPO production in humans."],["dc.identifier.doi","10.1007/s004240051012"],["dc.identifier.isi","000086460400021"],["dc.identifier.pmid","10784360"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16580"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0031-6768"],["dc.title","Dose-dependent effect of angiotensin II on human erythropoietin production"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","102989"],["dc.bibliographiccitation.journal","EBioMedicine"],["dc.bibliographiccitation.volume","60"],["dc.contributor.author","Danielyan, Lusine"],["dc.contributor.author","Schwab, Matthias"],["dc.contributor.author","Siegel, Georg"],["dc.contributor.author","Brawek, Bianca"],["dc.contributor.author","Garaschuk, Olga"],["dc.contributor.author","Asavapanumas, Nithi"],["dc.contributor.author","Buadze, Marine"],["dc.contributor.author","Lourhmati, Ali"],["dc.contributor.author","Wendel, Hans-Peter"],["dc.contributor.author","Avci-Adali, Meltem"],["dc.contributor.author","Krueger, Marcel A."],["dc.contributor.author","Calaminus, Carsten"],["dc.contributor.author","Naumann, Ulrike"],["dc.contributor.author","Winter, Stefan"],["dc.contributor.author","Schaeffeler, Elke"],["dc.contributor.author","Spogis, Annett"],["dc.contributor.author","Beer-Hammer, Sandra"],["dc.contributor.author","Neher, Jonas J."],["dc.contributor.author","Spohn, Gabriele"],["dc.contributor.author","Kretschmer, Anja"],["dc.contributor.author","Krämer-Albers, Eva-Maria"],["dc.contributor.author","Barth, Kerstin"],["dc.contributor.author","Lee, Hong Jun"],["dc.contributor.author","Kim, Seung U."],["dc.contributor.author","Frey, William H."],["dc.contributor.author","Claussen, Claus D."],["dc.contributor.author","Hermann, Dirk M."],["dc.contributor.author","Doeppner, Thorsten R."],["dc.contributor.author","Seifried, Erhard"],["dc.contributor.author","Gleiter, Christoph H."],["dc.contributor.author","Northoff, Hinnak"],["dc.contributor.author","Schäfer, Richard"],["dc.date.accessioned","2021-04-14T08:23:30Z"],["dc.date.available","2021-04-14T08:23:30Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.ebiom.2020.102989"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80939"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.issn","2352-3964"],["dc.title","Cell motility and migration as determinants of stem cell efficacy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","19"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","PHARMACOGENETICS"],["dc.bibliographiccitation.lastpage","26"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Kirchheiner, Julia"],["dc.contributor.author","Ufer, M."],["dc.contributor.author","Walter, E. C."],["dc.contributor.author","Kammerer, B."],["dc.contributor.author","Kahlich, R."],["dc.contributor.author","Meisel, C."],["dc.contributor.author","Schwab, M."],["dc.contributor.author","Gleiter, Christoph H."],["dc.contributor.author","Rane, A."],["dc.contributor.author","Roots, Ivar"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.date.accessioned","2018-11-07T10:53:02Z"],["dc.date.available","2018-11-07T10:53:02Z"],["dc.date.issued","2004"],["dc.description.abstract","CYP2C9 catalyses the biotransformation of the oral anticoagulants S-warfarin and R- and S-acenocoumarol. According to data obtained in vitro, phenprocoumon is also metabolized by CYP2C9 but the impact of the CYP2C9 polymorphism on phenprocoumon pharmacolkinetics has not been studied. Twenty-six healthy heterozygous and homozygous carriers of the CYP2C9 alleles 1 (wild-type), 2 (Arg144Cys), and 3 (lle359Leu) received a single oral dose of 12 mg of racemic phenprocoumon. Plasma and 12 h urine concentrations of both enantiomers and their monohydroxylated metabolites were measured by high-performance liquid chromatography with mass spectrometry detection. No significant effect of the CYP2C9 variants 2 and 3 on R-phenprocoumon pharmacokinetic parameters was detected, but S-phenprocoumon clearance tended to decrease with increasing number of CYP2C9 2 and 3 alleles. The ratios of S- to R-phenprocoumon plasma clearances were higher with a median of 0.95 in carriers of 1/ 1 versus 0.65 in 3/ 3 (P<0.001 for trend). Plasma and urine concentrations of 4'-, 6- and 7-hydroxyphenprocoumon were significantly lower in homozygous carriers of the CYP2C9 2 and 3 variants compared to CYP2C9 1/ 1. Carriers of CYP2C9 3/ 3 had a median AUC of (R,S) 7-OH-phenprocoumon of only approximately 25% compared to the wild-type genotype. The AUC of (R,S) 6-OH-phenprocoumon was only approximately 50% in CYP2C9 3/ 3 compared to the homozygous wild-type genotype. In conclusion, carriers of CYP2C9 2 and 3 alleles had a lower metabolic capacity regarding phenprocoumon hydroxylation than those with CYP2C9 1/ 1. However, regarding phenprocoumon hydroxylation CYP2C9 genotypes had only marginal effects on S- and R-phenprocoumon total clearance in healthy volunteers. Pharmacogenetics 14:19-26 (C) 2004 Lippincott Williams Wilkins."],["dc.identifier.doi","10.1097/00008571-200401000-00002"],["dc.identifier.isi","000189288800002"],["dc.identifier.pmid","15128047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49259"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0960-314X"],["dc.title","Effects of CYP2C9 polymorphisms on the pharmacokinetics of R- and S-phenprocournon in healthy volunteers"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4044"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","4049"],["dc.bibliographiccitation.volume","98"],["dc.contributor.author","Sirén, Anna-Leena"],["dc.contributor.author","Fratelli, Maddalena"],["dc.contributor.author","Brines, Michael"],["dc.contributor.author","Goemans, Christoph"],["dc.contributor.author","Casagrande, Simona"],["dc.contributor.author","Lewczuk, Pjotr"],["dc.contributor.author","Keenan, Sonja"],["dc.contributor.author","Gleiter, Christoph H."],["dc.contributor.author","Pasquali, Claudio"],["dc.contributor.author","Capobianco, Annalisa"],["dc.contributor.author","Mennini, Tiziana"],["dc.contributor.author","Heumann, Rolf"],["dc.contributor.author","Cerami, Anthony"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Ghezzi, Pietro"],["dc.date.accessioned","2018-03-08T09:22:11Z"],["dc.date.available","2018-03-08T09:22:11Z"],["dc.date.issued","2001"],["dc.description.abstract","Erythropoietin (EPO) promotes neuronal survival after hypoxia and other metabolic insults by largely unknown mechanisms. Apoptosis and necrosis have been proposed as mechanisms of cellular demise, and either could be the target of actions of EPO. This study evaluates whether antiapoptotic mechanisms can account for the neuroprotective actions of EPO. Systemic administration of EPO (5,000 units/kg of body weight, i.p.) after middle-cerebral artery occlusion in rats dramatically reduces the volume of infarction 24 h later, in concert with an almost complete reduction in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling of neurons within the ischemic penumbra. In both pure and mixed neuronal cultures, EPO (0.1–10 units/ml) also inhibits apoptosis induced by serum deprivation or kainic acid exposure. Protection requires pretreatment, consistent with the induction of a gene expression program, and is sustained for 3 days without the continued presence of EPO. EPO (0.3 units/ml) also protects hippocampal neurons against hypoxia-induced neuronal death through activation of extracellular signal-regulated kinases and protein kinase Akt-1/protein kinase B. The action of EPO is not limited to directly promoting cell survival, as EPO is trophic but not mitogenic in cultured neuronal cells. These data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries. The neurotrophic actions suggest there may be longer-latency effects as well. Evaluation of EPO, a compound established as clinically safe, as neuroprotective therapy in acute brain injury is further supported."],["dc.identifier.doi","10.1073/pnas.051606598"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/12910"],["dc.language.iso","en"],["dc.notes.intern","GRO-Li-Import"],["dc.notes.status","final"],["dc.relation.doi","10.1073/pnas.051606598"],["dc.relation.issn","0027-8424"],["dc.relation.issn","1091-6490"],["dc.title","Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","57"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","PHARMACOLOGY & TOXICOLOGY"],["dc.bibliographiccitation.lastpage","63"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","Schmidt, H."],["dc.contributor.author","Vormfelde, Stefan Viktor"],["dc.contributor.author","Klinder, K."],["dc.contributor.author","Gundert-Remy, Ursula"],["dc.contributor.author","Gleiter, Christoph H."],["dc.contributor.author","Skopp, G."],["dc.contributor.author","Aderjan, R."],["dc.contributor.author","Fuhr, Uwe"],["dc.date.accessioned","2018-11-07T10:17:35Z"],["dc.date.available","2018-11-07T10:17:35Z"],["dc.date.issued","2002"],["dc.description.abstract","Dihydrocodeine is metabolized to dihydromorphine, dihydrocodeine-6-O-, dihydromorphine-3-O- and dihydromorphine-6-O-glucuronide, and nordihydrocodeine. The current study was conducted to evaluate the affinities of dihydrocodeine and its metabolites to mu-, delta- and kappa-opioid receptors. Codeine, morphine, d,l-methadone and levomethadone were used as controls. Displacement binding experiments were carried out at the respective opioid receptor types using preparations of guinea pig cerebral cortex and the specific opioid agonists [H-3]DAMGO (g-opioid receptor), [H-3]DPDPE (8-opioid receptor) and [H-3]U69,593 (K-opioid receptor) as radioactive ligands at concentrations of 0.5, 1.0 and 1.0 nmol/l, respectively All substances had their greatest affinity to the mu-opioid receptor. The affinities of dihydromorphine and dihydromorphine-6-O-glucuronide were at least 70 times greater compared with dihydrocodeine (K-i 0.3 mumol/1), whereas the other metabolites yielded lower affinities. For the 6-opioid receptor, the order of affinities was similar with the exception that dihydrocodeine-6-O-glucuronide revealed a doubled affinity in relation to dihydrocodeine (K-i 5.9 mumol/1). In contrast, for the K-opioid receptor, dihydrocodeine-6-O- and dihydromorphine-6-O-glucuronide had clearly lower affinities compared to the respective parent compounds. The affinity of nordihydrocodeine was almost identical to that of dihydrocodeine (K-i 14 mumol/1), whereas dihydromorphine had a 60 times higher affinity. These results suggest that dihydromorphine and its 6-O-glucuronide may provide a relevant contribution to the pharmacological effects of dihydrocodeine. The O-demethylation of dihydrocodeine to dihydromorphine is mediated by the polymorphic cytochrome P450 enzyme CYP2D6, resulting in different metabolic profiles in extensive and poor metabolizers. About 7% of the caucasian population which are CYP2D6 poor metabolizers thus may experience therapeutic failure after standard doses."],["dc.identifier.doi","10.1034/j.1600-0773.2002.910203.x"],["dc.identifier.isi","000177528400003"],["dc.identifier.pmid","12420793"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41256"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Munksgaard"],["dc.relation.issn","0901-9928"],["dc.title","Affinities of dihydrocodeine and its metabolites to opioid receptors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","European Journal of Clinical Pharmacology"],["dc.bibliographiccitation.volume","58"],["dc.contributor.author","Simmenroth-Nayda, Anne"],["dc.contributor.author","Gleiter, Christoph H."],["dc.contributor.author","Niebling, W."],["dc.contributor.author","Hummers-Pradier, Eva"],["dc.contributor.author","Kochen, Michael M."],["dc.date.accessioned","2018-11-07T09:58:42Z"],["dc.date.available","2018-11-07T09:58:42Z"],["dc.date.issued","2002"],["dc.format.extent","S97"],["dc.identifier.isi","000179032800109"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37423"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","4th Annual Congress on Clinical Pharmacology"],["dc.relation.eventlocation","WIESBADEN, GERMANY"],["dc.relation.issn","0031-6970"],["dc.title","Switching brand name drugs to generic drugs in German general praxis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Stroke"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Hasselblatt, M."],["dc.contributor.author","Piotr, L."],["dc.contributor.author","Dembowski, C."],["dc.contributor.author","Cepek, L."],["dc.contributor.author","Stiefel, M."],["dc.contributor.author","Rustenbeck, Hans Heino"],["dc.contributor.author","Jacob, S."],["dc.contributor.author","Knerlich, F."],["dc.contributor.author","Gleiter, Christoph H."],["dc.contributor.author","Prange, Hilmar"],["dc.contributor.author","Siren, A. L."],["dc.date.accessioned","2018-11-07T10:33:49Z"],["dc.date.available","2018-11-07T10:33:49Z"],["dc.date.issued","2002"],["dc.format.extent","354"],["dc.identifier.isi","000173147700143"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44705"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.issn","0039-2499"],["dc.title","Erythropoietin treatment for acute stroke: A randomized double-blind proof-of concept trial in man"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","271"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","276"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Siren, A. L."],["dc.contributor.author","Knerlich, F."],["dc.contributor.author","Poser, Wolfgang"],["dc.contributor.author","Gleiter, Christoph H."],["dc.contributor.author","Bruck, Wolfgang W."],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2018-11-07T09:17:30Z"],["dc.date.available","2018-11-07T09:17:30Z"],["dc.date.issued","2001"],["dc.description.abstract","Using immunohistochemistry, expression of erythropoietin (EPO), a hypoxia-inducible neuroprotective factor, and its receptor (EPOR) were investigated in human brain tissue after ischemia/hypoxia. Autopsy brains of neuropathologically normal subjects were compared to those with ischemic infarcts or hypoxic damage. In normal brain, weak EPO/EPOR immunoreactivity was mainly neuronal. In fresh infarcts, EPO immunoreactivity appeared in vascular endothelium, EPOR in microvessels and neuronal fibers. In older infarcts reactive astrocytes exhibited EPO/EPOR immunoreactivity. Acute hypoxic brain damage was associated with vascular EPO expression, older hypoxic damage with EPO/EPOR immunoreactivity in reactive astrocytes. The pronounced up-regulation of EPO/EPOR in human ischemic/hypoxic brains underlines their role as an endogenous neuroprotective system and suggests a novel therapeutic potential in cerebrovascular disease for EPO, a clinically well-characterized and safe compound."],["dc.identifier.isi","000167526200013"],["dc.identifier.pmid","11307627"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28185"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0001-6322"],["dc.title","Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","253"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","European Journal of Clinical Pharmacology"],["dc.bibliographiccitation.lastpage","257"],["dc.bibliographiccitation.volume","58"],["dc.contributor.author","Meyer-Barner, M."],["dc.contributor.author","Meineke, Ingolf"],["dc.contributor.author","Schreeb, K. H."],["dc.contributor.author","Gleiter, Christoph H."],["dc.date.accessioned","2018-11-07T10:20:36Z"],["dc.date.available","2018-11-07T10:20:36Z"],["dc.date.issued","2002"],["dc.description.abstract","Objective: Little information on the population pharmacokinetics of the tricyclic antidepressant doxepine and its pharmacologically active metabolite desmethyldoxepine is available. However, a more individualised drug therapy may be feasible if the influence of various patient characteristics on plasma concentration was known. Patients and methods: We retrospectively analysed pharmacokinetic therapeutic drug-monitoring data in 114 psychiatric patients (79 females, 35 males) treated with doxepine for a period of 22-306 days, mostly due to major depression. The data were analysed using the computer program NONMEM. For both, doxepine and its metabolite desmethyldoxepine, a one-compartment model was chosen. Pharmacokinetic parameters clearance (CL/F) and volume of distribution (V/F) of doxepine and desmethyldoxepine were modelled in terms of both random and fixed effects. Results: The fit of the model to the concentration-time data was significantly improved when V/F was expressed as a function of weight (P < 0.05) and CL/F as a function of age (P < 0.05). Co-medication that inhibits P-450 isoenzymes lowered CL/F of doxepine by 15%. Conclusion: The analysis indicates that the factors age and, to some extent, body weight may be a guidance for individual doxepine dose regimens, which however needs confirmation in prospective clinical trials linking pharmacokinetics and therapeutic effect. Co-medication may represent only a minor important covariate."],["dc.identifier.doi","10.1007/s00228-002-0448-3"],["dc.identifier.isi","000177241500005"],["dc.identifier.pmid","12136371"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41918"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0031-6970"],["dc.title","Pharmacokinetics of doxepin and desmethyldoxepin: an evaluation with the population approach"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","592"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","British Journal of Clinical Pharmacology"],["dc.bibliographiccitation.lastpage","603"],["dc.bibliographiccitation.volume","54"],["dc.contributor.author","Meineke, Ingolf"],["dc.contributor.author","Freudenthaler, S."],["dc.contributor.author","Hofmann, U."],["dc.contributor.author","Schaeffeler, E."],["dc.contributor.author","Mikus, G."],["dc.contributor.author","Schwab, M."],["dc.contributor.author","Prange, H. W."],["dc.contributor.author","Gleiter, Christoph H."],["dc.contributor.author","Brockmoeller, Juergen"],["dc.date.accessioned","2018-11-07T09:43:46Z"],["dc.date.available","2018-11-07T09:43:46Z"],["dc.date.issued","2002"],["dc.description.abstract","Aims Concentrations in the cerebrospinal fluid (CSF) are a useful approximation to the effect site for drugs like morphine. However, CSF samples, are available only in rare circumstances. If they can be obtained they may provide important insights into the pharmacokinetics/pharmacodynamics of opioids. Methods Nine neurological and neurosurgical patients (age 19-69 years) received 0.5 mg kg(-1) morphine sulphate pentahydrate as an intravenous infusion over 30 min. Plasma and CSF were collected for up to 48 h. Concentration time-course and interindividual variability of morphine (M), morphine-3-glucuronide (M3G) and morphine-6 glucuronide (M6G) were analysed using population pharmacokinetic modelling. Results While morphine was rapidly cleared from plasma (total clearance = 1838 ml min(-1) (95% CI 1668, 2001 ml min(-1) )) the glucuronide metabolites were eliminated more slowly (clearance M3G = 44.5 ml min(-1) (35.1, 53.9 ml min(-1) ), clearance M6G = 42.1 ml min(-1) (36.4, 47.7 ml min(-1) )) and their clearance could be described as a function of creatinine clearance. The central volumes of distribution were estimated to be 12.7 l (11.1, 14.3 l) for morphine. Transfer from the central compartment into the CSF was also rapid for M and considerably slower for both glucuronide metabolites. Maximum concentrations were achieved after 102 min (M), 417 min (M3G) and 443 min (M6G). A P-glycoprotein exon 26 polymorphism previously found to be linked with transport activity could be involved in CSF accessibility, since the homozygous mutant genotype was associated (P < 0.001) with high maximum CSF concentrations of M but not M3G or M6G. Conclusions From the population pharmacokinetic model presented, CSF concentration profiles can be derived for M, M3G and M6G on the basis of dosing information and creatinine clearance without collecting CSF samples. Such profiles may then serve as the link between dose regimen and effect measurements in future clinical effect studies."],["dc.identifier.doi","10.1046/j.1365-2125.2002.t01-1-01689.x"],["dc.identifier.isi","000179909500005"],["dc.identifier.pmid","12492606"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34251"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing Ltd"],["dc.relation.issn","0306-5251"],["dc.title","Pharmacokinetic modelling of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]