Ostergaard D

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Full name : Ostergaard Doris

First name : Doris

Mail : Department of Anaesthesia. Glostrup Hospital, Nordre Ringues, 2600 Glostrup. Copenhagen

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Country : Denmark

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Phone : (45) 42 964 333

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References (15)

Title : Influence of plasma cholinesterase activity and phenotype on the pharmacodynamics and pharmacokinetics of mivacurium -
Author(s) : Ostergaard D
Ref : Acta Anaesthesiologica Scandinavica , 51 :773 , 2007
PubMedID:

Title : Pharmacokinetics and pharmacodynamics of mivacurium in patients phenotypically homozygous for the atypical plasma cholinesterase variant: effect of injection of human cholinesterase - Ostergaard_2005_Anesthesiology_102_1124
Author(s) : Ostergaard D , Viby-Mogensen J , Rasmussen SN , Gatke MR , Varin F
Ref : Anesthesiology , 102 :1124 , 2005
Abstract : BACKGROUND: In patients homozygous for atypical plasma cholinesterase, mivacurium causes a long-lasting neuromuscular block, but injection of human cholinesterase has been proven effective in antagonizing the block. The purpose of this study was to evaluate the pharmacodynamics and pharmacokinetics of mivacurium in such patients, as well as the effect of cholinesterase injected early or late after mivacurium.
METHODS: Eleven patients phenotypically homozygous for the atypical variant received 0.075 mg/kg (1 patient) or 0.15 mg/kg (10 patients) mivacurium. The neuromuscular block was monitored using train-of-four nerve stimulation and mechanomyography. Cholinesterase, 2.8-10.0 mg/kg, was administered approximately 30 or 120 min after mivacurium. The times to different levels of neuromuscular recovery and the venous concentrations of the isomers of mivacurium were measured.
RESULTS: Injection of cholinesterase increased plasma cholinesterase activity to normal and the clearances of the active isomers and the elimination rate constants by a factor of 10-15. The first response was seen in 13.5 min (3.7-44.2 min). Time to a train-of-four ratio of 0.8 ranged from 30 to 60 min (n = 6). Neostigmine injected after cholinesterase shortened recovery further, and a train-of-four ratio of 0.8 was reached in 10-30 min. CONCLUSION: As expected, the duration of action of mivacurium is markedly prolonged in homozygous atypical patients. Injection of cholinesterase significantly increases the metabolism of mivacurium, leading to a shorter duration of action. Injection of neostigmine after the administration of cholinesterase speeds up recovery.
ESTHER : Ostergaard_2005_Anesthesiology_102_1124
PubMedSearch : Ostergaard_2005_Anesthesiology_102_1124
PubMedID: 15915024

Title : Response to mivacurium in patients carrying the k variant in the butyrylcholinesterase gene - Gatke_2005_Anesthesiology_102_503
Author(s) : Gatke MR , Viby-Mogensen J , Ostergaard D , Bundgaard JR
Ref : Anesthesiology , 102 :503 , 2005
Abstract : BACKGROUND: Mivacurium is hydrolyzed by the butyrylcholinesterase enzyme, and patients with hereditary changes of the enzyme often have prolonged duration of action of mivacurium. In this study, the authors investigated the significance of the most commonly occurring variant, the Kalow (K) variant, established using DNA analysis, for the response to mivacurium.
METHODS: A total of 58 patients carrying either the wild-type butyrylcholinesterase or different combinations of the atypical (A) variant and the K variant were included. Patients who were homozygous for the A variant were given 0.03 mg/kg mivacurium. All other patients received 0.2 mg/kg mivacurium. The neuromuscular block was measured using train-of-four nerve stimulation and mechanomyography. Genotyping was performed with complete nucleotide sequencing.
RESULTS: Heterozygosity of the K variant prolonged the time to train-of-four 0.70 from 26.6 to 34.5 min (30%; not significant) as compared with the wild type. Heterozygosity of the K variant linked to the A variant prolonged the corresponding time from 32 to 42.7 min (33%; P = 0.03) as compared with patients who were heterozygous for solely an A allele. For eight patients who were homozygous for both the A and K variants, the time to 25% recovery was 78-89 min as compared with 44-57 min in patients who were homozygous for the A variant or had only one linked K variant. CONCLUSION: The K variant prolongs the duration of action of mivacurium. The current results indicate that the effect is modest when the K variant occurs heterozygously with the wild type or the A variant but is marked in patients who are homozygous for both the A and K variants.
ESTHER : Gatke_2005_Anesthesiology_102_503
PubMedSearch : Gatke_2005_Anesthesiology_102_503
PubMedID: 15731585

Title : Pharmacokinetics and pharmacodynamics of mivacurium in patients phenotypically heterozygous for the usual and atypical plasma cholinesterase variants (UA) - Ostergaard_2003_Acta.Anaesthesiol.Scand_47_1219
Author(s) : Ostergaard D , Viby-Mogensen J , Rasmussen SN , Gatke MR , Pedersen NA , Skovgaard LT
Ref : Acta Anaesthesiologica Scandinavica , 47 :1219 , 2003
Abstract : BACKGROUND: Mivacurium is hydrolyzed by plasma cholinesterase (pChe). The purpose of this study was to evaluate the pharmacodynamics and the pharmacokinetics of the three isomers of mivacurium in patients phenotypically heterozygous for the usual and the atypical pChe variant (UA).
METHODS: Thirty-two patients were included in a dose-response study, in which the patients received one of four doses of mivacurium. An additional bolus dose of mivacurium, to a total of 0.1 mg kg-1, was given followed by a continuous infusion adjusted to maintain 91-99% neuromuscular block. The times to different levels of recovery following the infusion were measured using mechanomyography and train-of-four (TOF) nerve stimulation. Twelve of the patients with an estimated duration of anaesthesia of more than 90 min were (randomly) selected for the pharmacokinetic part of the study. Venous samples were taken for determination of the three isomers of mivacurium. These results were compared with results from a previous study in phenotypically normal patients (UU).
RESULTS: The estimated ED50 and ED95 were 24 and 69 microg kg-1, respectively. The median (range) infusion rate was 3.7 microg kg-1 min-1 (1.2-2.9) and the time to a TOF ratio of 0.7 was 29.8 min (16.1-44.8). The median clearances of the cis-cis, cis-trans and trans-trans isomers were 3.7, 29 and 28 ml kg-1 min-1, respectively. The elimination half-lives of the isomers were 45, 6.7 and 6.3 min, respectively. CONCLUSION: In patients heterozygous for the usual and the atypical variant (UA), the potency of mivacurium is higher, the infusion requirements lower and the rate of spontaneous recovery prolonged, compared with phenotypically normal patients. The clearances of the active isomers are significantly lower and the elimination half-lives longer in heterozygous patients than in phenotypically normal patients (UU). The pharmacokinetics of the inactive cis-cis isomer was not affected.
ESTHER : Ostergaard_2003_Acta.Anaesthesiol.Scand_47_1219
PubMedSearch : Ostergaard_2003_Acta.Anaesthesiol.Scand_47_1219
PubMedID: 14616318

Title : The pharmacodynamics and pharmacokinetics of mivacurium in children - Ostergaard_2002_Acta.Anaesthesiol.Scand_46_512
Author(s) : Ostergaard D , Gatke MR , Berg H , Rasmussen SN , Viby-Mogensen J
Ref : Acta Anaesthesiologica Scandinavica , 46 :512 , 2002
Abstract : BACKGROUND: In children, onset time and duration of action of mivacurium are shorter than in adults. Some suggest that this is due to differences in plasma cholinesterase (pChe), whereas others indicate that there is no difference. The purpose of this study was to evaluate the pharmacodynamics and pharmacokinetics of mivacurium in phenotypically normal children aged 3-6 and 10-14 years old, respectively.
METHODS: Ten children aged 3-6 years and 10 children aged 10-14 years were studied during halothane anaesthesia. Before induction of anaesthesia, a blood sample was drawn to measure the pChe activity and phenotype. The neuromuscular block was monitored at the thumb using train-of-four (TOF) nerve stimulation every 12 s and mechanomyography. The times to different levels of neuromuscular recovery following mivacurium 0.2 mg/kg were recorded. The concentrations in venous blood of the three isomers and the metabolites of mivacurium were measured.
RESULTS: No statistically significant difference was found in pChe activity or in the pharmacodynamics of mivacurium. The onset time was 1.4 min (0.8-1.9) median (range) and 1.3 min (1.1-1.9) and the time to first response to TOF nerve stimulation was 9.6 min (6.5-12.6) and 10.5 min (7.0-14.0) in young and older children, respectively. The pharmacokinetic data were too sparse to allow analysis of the two age groups separately (8 and 8 patients), hence the data were pooled. The median clearances of the cis-cis, the cis-trans, and the trans-trans isomer were 5.5, 51.0 and 30.5 ml/kg/min, respectively. CONCLUSION: Our data indicate that there are no major differences in pharmacodynamics or pharmacokinetics of mivacurium between young (3-6 years) and older (10-14 years) children.
ESTHER : Ostergaard_2002_Acta.Anaesthesiol.Scand_46_512
PubMedSearch : Ostergaard_2002_Acta.Anaesthesiol.Scand_46_512
PubMedID: 12027844

Title : Response to mivacurium in a patient compound heterozygous for a novel and a known silent mutation in the butyrylcholinesterase gene: genotyping by sequencing - Gatke_2001_Anesthesiology_95_600
Author(s) : Gatke MR , Ostergaard D , Bundgaard JR , Varin F , Viby-Mogensen J
Ref : Anesthesiology , 95 :600 , 2001
Abstract : BACKGROUND Patients who are homozygous for the atypical mutation, compound heterozygous for atypical and silent mutations, or homozygous for silent mutations (SS) respond to mivacurium with extensively prolonged neuromuscular block. Although important, exact phenotyping of these patients is difficult. This article presents the pharmacodynamics and pharmacokinetics of a normal dose of mivacurium in a patient with phenotype SS, including a pedigree analysis and delineation of the molecular genetic method used to identify the genotype. METHODS: The neuromuscular block following administration of mivacurium, at a dose of 0.14 mg/kg, was monitored in a 30-yr-old healthy man with use of a mechanosensor and mechanomyography, and times to different levels of recovery were measured. Venous samples for determination of the mivacurium isomers were collected during the interval 134-494 min after administration of mivacurium, and the terminal half-lives were calculated. Butyrylcholinesterase activity, phenotype, and genotype were determined for both the patient and the family. Complete nucleotide sequencing was used to identify the genotype. RESULTS: A train-of-four ratio of 0.75 was reached 469 min after the injection of mivacurium. The terminal elimination half-lives of the mivacurium isomers, cis-trans and trans-trans, were 90 min. Complete nucleotide sequencing revealed two point mutations, the known silent variant S7 and a previously undescribed mutation of amino acid residue 170 introducing a stop codon.
CONCLUSIONS: The patient was compound heterozygous for silent mutations in the butyrylcholinesterase gene. The response to mivacurium was an extensively prolonged duration of action. Identification of the rare silent mutations presupposes access to modern molecular genetic methods such as complete nucleotide sequencing.
ESTHER : Gatke_2001_Anesthesiology_95_600
PubMedSearch : Gatke_2001_Anesthesiology_95_600
PubMedID: 11575530

Title : The influence of drug-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium - Ostergaard_2000_Anesthesiology_92_1581
Author(s) : Ostergaard D , Rasmussen SN , Viby-Mogensen J , Pedersen NA , Boysen R
Ref : Anesthesiology , 92 :1581 , 2000
Abstract : BACKGROUND: The short duration of action of mivacurium results from its rapid hydrolysis by plasma cholinesterase. Bambuterol, an oral bronchodilator, has an inhibiting effect on plasma cholinesterase. The purpose of this study was to evaluate the effect of bambuterol-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium.
METHODS: Fourteen patients received 20 mg bambuterol and 14 patients received placebo orally 2 h before induction of anesthesia. During anesthesia the neuromuscular block was monitored at the thumb using train-of-four nerve stimulation every 12 s and mechanomyography. The times to different levels of neuromuscular recovery after 0.2 mg/kg mivacurium were measured. The concentrations in venous blood of the three isomers and the metabolites of mivacurium were measured using high-performance liquid chromatography.
RESULTS: Plasma cholinesterase activity was inhibited a median of 90% (range, 67-97%) after bambuterol. The time to first response to train-of-four nerve stimulation was 15 min (range, 9-21 min) and 59 min (range, 32-179 min) in patients receiving placebo and bambuterol, respectively. The estimated clearances of the isomers were significantly lower and the elimination half-lives of all three isomers significantly prolonged in patients receiving bambuterol. No difference was seen in elimination half-lives of the metabolites. The elimination rate constant from the effect compartment and the potency of mivacurium was not affected by bambuterol. CONCLUSION: A 90% inhibition of plasma cholinesterase activity significantly reduced clearance of the isomers of mivacurium. Correspondingly, the duration of action of 0.2 mg/kg mivacurium was prolonged three- to fourfold, compared with patients not administered bambuterol.
ESTHER : Ostergaard_2000_Anesthesiology_92_1581
PubMedSearch : Ostergaard_2000_Anesthesiology_92_1581
PubMedID: 10839906

Title : [Mutation of the plasma cholinesterase gene and anesthesia. Information from the Danish Cholinesterase Registry] -
Author(s) : Jensen FS , Gatke MR , Ostergaard D , Bundgaard JR , Mogensen JV
Ref : Ugeskr Laeger , 162 :161 , 2000
PubMedID: 10647312

Title : Reversal of intense mivacurium block with human plasma cholinesterase in patients with atypical plasma cholinesterase - Ostergaard_1995_Anesthesiology_82_1295
Author(s) : Ostergaard D , Jensen FS , Viby-Mogensen J
Ref : Anesthesiology , 82 :1295 , 1995
Abstract :
ESTHER : Ostergaard_1995_Anesthesiology_82_1295
PubMedSearch : Ostergaard_1995_Anesthesiology_82_1295
PubMedID: 7741307

Title : Dose-response relationship for mivacurium in patients with phenotypically abnormal plasma cholinesterase activity [see comments] - Ostergaard_1995_Acta.Anaesthesiol.Scand_39_1016
Author(s) : Ostergaard D , Jensen FS , Skovgaard LT , Viby-Mogensen J
Ref : Acta Anaesthesiologica Scandinavica , 39 :1016 , 1995
Abstract : During thiopentone-fentanyl-nitrous oxide anaesthesia and using a cumulative design, we studied the dose-response relationship of mivacurium in 8 patients: 7 patients phenotypically homozygous for the atypical plasma cholinesterase gene and 1 patient homozygous for the silent gene. The estimated mean ED50 and ED95 were 15 and 20 micrograms.kg.bw-1 in patients homozygous for the atypical gene, and 13 and 16 micrograms.kg.bw-1 in the patient homozygous for the silent gene, respectively. The results indicate that mivacurium is 4-5 times more potent in patients homozygous for the atypical or the silent gene than in patients with normal plasma cholinesterase activity and phenotype.
ESTHER : Ostergaard_1995_Acta.Anaesthesiol.Scand_39_1016
PubMedSearch : Ostergaard_1995_Acta.Anaesthesiol.Scand_39_1016
PubMedID: 8607300

Title : Mivacurium-induced neuromuscular blockade in patients with atypical plasma cholinesterase - Ostergaard_1993_Acta.Anaesthesiol.Scand_37_314
Author(s) : Ostergaard D , Jensen FS , Jensen E , Skovgaard LT , Viby-Mogensen J
Ref : Acta Anaesthesiologica Scandinavica , 37 :314 , 1993
Abstract : The duration of action of mivacurium was evaluated during a modified neurolept anaesthesia in 17 patients heterozygous for the usual and the atypical plasma cholinesterase (pChe) gene (E1uE1a) and in five patients homozygous for the atypical gene (E1aE1a). The response to train-of-four nerve stimulation was recorded using a Myograph 2000. Five heterozygous patients were given a small dose of mivacurium 0.03 mg kg bw-1 intravenously (Group 1). The mean (range) suppression of the first twitch in the train-of-four response (T1) was 91% (69-100%). The time to 90% T1 recovery was 23.9 min (14.0-31.3 min). Twelve other heterozygous patients (Group 2) received mivacurium 0.2 mg kg bw-1 (2.5 x ED95). In these patients the time to 100% T1 suppression was 1.4 min (1.1-2.0 min). The time to reappearance of the T1 response, to 90% T1 recovery, and the recovery index (25.3 min (14.5-34.5), 45.5 min (30.9-59.2), and 9.8 min (6.8-19.6), respectively) were significantly longer than reported in phenotypically normal patients. Five patients homozygous for the atypical gene (Group 3) were given 0.03 mg kg bw-1 mivacurium. The time to reappearance of T1 response following this low dose of mivacurium ranged from 26-128 min. In all five patients the neuromuscular block was successfully antagonized with neostigmine preceded by atropine. In conclusion, mivacurium-induced neuromuscular blockade was moderately prolonged in patients heterozygous for the usual and the atypical gene for plasma cholinesterase. Patients homozygous for the atypical plasma cholinesterase gene appear to be markedly sensitive to mivacurium.
ESTHER : Ostergaard_1993_Acta.Anaesthesiol.Scand_37_314
PubMedSearch : Ostergaard_1993_Acta.Anaesthesiol.Scand_37_314
PubMedID: 8390770

Title : Influence of plasma cholinesterase activity on recovery from mivacurium-induced neuromuscular blockade in phenotypically normal patients - Ostergaard_1992_Acta.Anaesthesiol.Scand_36_702
Author(s) : Ostergaard D , Jensen FS , Jensen E , Skovgaard LT , Viby-Mogensen J
Ref : Acta Anaesthesiologica Scandinavica , 36 :702 , 1992
Abstract : The significance of plasma cholinesterase (pChe) activity for the duration of action of mivacurium in phenotypically normal patients was evaluated in 35 patients during neurolept anaesthesia. The response to train-of-four nerve stimulation was recorded using a Myograph 2000. Ten patients with normal pChe (Group I) and five patients with decreased pChe activity (Group 2) were given a small test dose of mivacurium 0.03 mg kg-1. Mivacurium 0.1 mg kg-1 was administered following spontaneous recovery from the first dose. The mean suppression of the height of the first (T1) of the train-of-four responses following mivacurium 0.03 mg kg-1 patients with normal and decreased enzyme activity was 40% and 56%, respectively, and the mean T1 suppression after mivacurium 0.1 mg kg-1 was 100% in both groups. The times to different levels of twitch height recovery following the 0.1 mg kg-1 dose did not differ between the two groups of patients. Another 20 patients with normal or decreased pChe activity (Group 3) were given mivacurium 0.2 mg kg-1. In this group the time to maximum block was 1.4 min (1.0-4.0) mean (range) and the time to reappearance of the T1 response was 15.0 min (7.4-22.7) (range). An inverse relationship was found between the patients' pChe activity and the time to first response. It is concluded that mivacurium is short-acting in patients with normal pChe phenotype and normal to low-normal pChe activity. No patient with very low pChe activity was included in the study. A prolonged response to mivacurium may, however, be expected in these patients.
ESTHER : Ostergaard_1992_Acta.Anaesthesiol.Scand_36_702
PubMedSearch : Ostergaard_1992_Acta.Anaesthesiol.Scand_36_702
PubMedID: 1441874

Title : Pretreatment with pancuronium before suxamethonium administration in patients heterozygous for the usual and the atypical plasma cholinesterase gene - Ostergaard_1991_Acta.Anaesthesiol.Scand_35_502
Author(s) : Ostergaard D , Viby-Mogensen J , Hanel HK , Skovgaard LT
Ref : Acta Anaesthesiologica Scandinavica , 35 :502 , 1991
Abstract : The object of this study was to investigate whether pretreatment with pancuronium before i.v. injection of suxamethonium could cause prolonged neuromuscular blockade in patients heterozygous for the usual and the atypical plasma cholinesterase gene (E1uE1a). Forty-three patients, 23 with genotype E1uE1a and 20 with normal genotype (E1uE1u), were pretreated with pancuronium 0.01 mg.kg-1 followed by suxamethonium 1.5 mg.kg-1, and received either neurolept anaesthesia or halothane anaesthesia. Seven patients (E1uE1a) were given suxamethonium 1.5 mg.kg-1 without pretreatment. The duration and type of neuromuscular block were evaluated using train-of-four (TOF) nerve stimulation. Type of anaesthesia did not significantly influence the results. The duration of block following pretreatment was significantly longer in heterozygous patients than in normal patients. Time to 90% twitch height recovery was 10.7 +/- 1.2 min (mean +/- s.d.) in genotypically normal patients, and 18.0 +/- 4.2 min in patients with genotype E1uE1a. Pretreatment with pancuronium caused a significantly slower recovery of the TOF ratio (phase II block). Thus, a TOF ratio of 0.7 was always reached within 13 min in genotypically normal patients. In genotypically abnormal patients, the same TOF ratio was reached within 20 min in all but three patients. In these three patients time to 90% twitch height recovery was prolonged (18-31 min), and TOF ratio did not return to normal, but stabilized at about 0.35, 0.50, and 0.65, respectively. Injection of edrophonium restored normal neuromuscular function in 10 min. It is concluded that in patients heterozygous for the usual and the atypical gene, pretreatment with pancuronium in combination with an increased dose of suxamethonium may cause a phase II block and thus a prolonged neuromuscular block.
ESTHER : Ostergaard_1991_Acta.Anaesthesiol.Scand_35_502
PubMedSearch : Ostergaard_1991_Acta.Anaesthesiol.Scand_35_502
PubMedID: 1897345

Title : Adverse reactions and interactions of the neuromuscular blocking drugs - Ostergaard_1989_Med.Toxicol.Adverse.Drug.Exp_4_351
Author(s) : Ostergaard D , Engbaek J , Viby-Mogensen J
Ref : Med Toxicol Adverse Drug Exp , 4 :351 , 1989
Abstract : The adverse reactions seen following administration of neuromuscular blocking agents are mainly cardiovascular. Due to the lack of specificity for the nicotinic receptor at the neuromuscular junction, these agents may interact with receptors in autonomic ganglia and muscarinic receptors in the heart. Furthermore, muscle relaxants may have histamine-releasing properties. The cardiovascular effects vary with potency and specificity of the drug, depending mainly on the chemical structure. Pancuronium, fazadinium and especially gallamonium block cardiac muscarinic receptors, and tachycardia may be seen. Atracurium, metocurine and in particular d-tubocurarine have histamine-releasing properties and may cause flushing, hypotension and tachycardia. Vecuronium has no effect on the cardiovascular system. The effect of succinylcholine on heart rate differs between children, where bradycardia is seen, and adults in whom tachycardia may follow. However, bradycardia may occur in adults following a single dose. Succinylcholine increases plasma potassium, especially in patients with nerve damage, and arrhythmias may be observed. The neuromuscular adverse effects of succinylcholine, such as fasciculations and increased gastric and intraocular pressure, may be prevented by precurarisation. Many drugs interact with neuromuscular blocking agents and there is often a potentiation of the neuromuscular effect. This is of clinical importance in the case of antibiotics, inhalational anaesthetics, lithium and cyclosporin. Difficulty in reversing the block may occur with calcium channel blockers and polymyxin. However, some drugs, such as phenytoin, carbamazepine and lithium, may cause resistance to neuromuscular blocking agents. Furthermore, clinically important interactions exist between individual neuromuscular blocking drugs. Precurarisation with a non-depolarising drug prolongs the onset of succinylcholine, and conversely a prolonged effect of non-depolarising drugs is seen following succinylcholine. The effect of succinylcholine is markedly prolonged if the drug is administered during recovery from pancuronium blockade or following neostigmine for reversal. Succinylcholine is hydrolysed by plasma cholinesterase, and drugs which decrease the activity of this enzyme may produce a prolonged block, i.e. contraceptive pills, cyclophosphamide, echothiopate and organophosphate.
ESTHER : Ostergaard_1989_Med.Toxicol.Adverse.Drug.Exp_4_351
PubMedSearch : Ostergaard_1989_Med.Toxicol.Adverse.Drug.Exp_4_351
PubMedID: 2682131

Title : Half-life of plasma cholinesterase - Ostergaard_1988_Acta.Anaesthesiol.Scand_32_266
Author(s) : Ostergaard D , Viby-Mogensen J , Hanel HK , Skovgaard LT
Ref : Acta Anaesthesiologica Scandinavica , 32 :266 , 1988
Abstract : The half-life of plasma cholinesterase (acylcholine acylhydrolase EC 3.1.1.8) was determined in three patients homozygous for the atypical gene for plasma cholinesterase by measuring the rate of disappearance of enzyme activity following intravenous injection of concentrated human cholinesterase. Half-life values of 10.9, 11.1, and 11.3 days were estimated. The distribution volume was estimated to be 18.0, 18.2, and 13.8% of body weight, respectively.
ESTHER : Ostergaard_1988_Acta.Anaesthesiol.Scand_32_266
PubMedSearch : Ostergaard_1988_Acta.Anaesthesiol.Scand_32_266
PubMedID: 3364151