Immunochemical Studies of Submicrosomal Membranes from Liver of Normal and Phenobarbital-Treated Rats

Lundkvist, U.; Perlmann, Peter

doi:10.1126/science.152.3723.780

Cited by 19 publications

(3 citation statements)

References 14 publications

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“…It is possible that the short length of PB pretreatment in this study may have underestimated the induction effect on hydrolysis. Results from other studies have suggested that rat liver esterase induction by PB is dependent on the dose and duration of pretreatment, and that different inducers have different magnitudes of effect on esterase induction (Lundkvist and Perlmann, 1966; Schwark and Ecobichon, 1968; Nousiainen and Hanninen, 1981). Nevertheless, current data is insufficient to ascertain an inducible effect of EIAEDs on LEV hydrolysis, but such an effect still cannot be ruled out and could explain our findings.…”

Section: Discussionmentioning

confidence: 97%

Effect of Age and Comedication on Levetiracetam Pharmacokinetics and Tolerability

et al. 2007

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Summary: Purpose:To compare pharmacokinetics and tolerability of levetiracetam (LEV) in older versus younger adults.Methods: As part of the Columbia Antiepileptic Drug Database, we retrospectively studied the pharmacokinetics and tolerability of LEV in patients who had been seen as an outpatient at our center during a 4-year period. We compared apparent clearance (CL) of LEV in the youngest (16-31 years; n = 151) and oldest (55-88 years; n = 157) quartile of 629 adult outpatients who had taken LEV. We also analyzed the frequency of adverse effects leading to dose change or discontinuation ("intolerability") and specific adverse effects in the younger versus older adults. One-year retention was determined for younger and older adults newly started on LEV at our center.Results: Mean LEV CL differed significantly between older (46.5 ml/h/kg) and younger adults (78.3 ml/h/kg). On average, older patients had a 40% lower LEV CL than younger patients. Comedication with an enzyme-inducing antiepileptic drug (EIAED; mostly carbamazepine) was associated with a 24% higher clearance of LEV compared to those who were not on EIAEDs. This difference was 37% in a subgroup of patients whose LEV CL was compared while they were on and off EIAEDs. Stepwise linear regression identified younger age and comedication with an EIAED as significant predictors of increased LEV CL. A total of 34.3% of the 629 patients (31.7% of younger vs. 40.7% of older patients; p = 0.16) reported intolerability to LEV on at least one occasion. This difference in tolerability reached significance in the group of patients newly started on LEV (26.3% vs. 41.0%; p = 0.017). Drowsiness and psychiatric/behavioral side effects were the most common adverse effects associated with LEV use in both age groups. Oneyear retention was 72% in the older group vs. 54% in the younger group (not significant).Conclusion: Older adults have lower CL than younger adults and require a mean 40% lower dose of LEV to achieve the same serum level. Comedication with an EIAED increases LEV CL by 24-37%. Younger adults tolerate LEV better than older adults, but 1-year retention was (nonsignificantly) higher in the older group.Seizures occur in an age dependent, bimodal pattern

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Section: Discussionmentioning

confidence: 97%

Effect of Age and Comedication on Levetiracetam Pharmacokinetics and Tolerability

et al. 2007

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“…Phenobarbital is known to induce hepatic microsomal esterase activity and also to modulate the esterase pattern in the rat (19,20). Phenobarbital pretreatment of mice acted differently upon the esterase activity with regard to the phenyl-propionic esters than to the acetic esters: the former substantially increased and the latter decreased ( Table III).…”

Section: Discussionmentioning

confidence: 99%

Structural parameters in the microsomal hydrolysis of 3-acyloxy-l, 4-benzodiazepines and the multiplicity of the esterases involved

Maksay

Tegyey

Simon‐Trompler

et al. 1980

European Journal of Drug Metabolism and Pharmacokinetics

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The biotransformation of several prodrug-type esters of centrally acting 1, 4-benzodiazepines was studied. Their rates of hydrolysis catalyzed by the hepatic microsomal fraction of mice were measured by pH-stat. The heterogeneity of the microsomal esterases was investigated with induction by phenobarbital and with inhibition by DFP. The resulting changes in esterase activity indicated that the phenyl-substituted esters separate from the homogenous sets of oxazepam and lorazepam esters. Regression analysis of the relative hydrolysis rates of the homogenous ester sets revealed a similar dependence on the steric ES the polar sigma* and hydrophobic deltaRM terms of the acyl moiety. The role of the polar term shows that a nucleophilic attack of the acyl moiety determines the hydrolysis. The role of hydrophobicity can be attributed to its interrelation with the steric parameter. The common equations for the aliphatic sters of oxazepam and larazepam suggest the similar nature of the esterases in question and the same catalytic mechanism. Different 3-acetoxy-1, 4-benzodiazepines were also synthetised and their maximal hydrolysis rates were quite different. This excludes the possibility that the deacylation step of the enzymes is rate-determining. Instead, our data suggest that acylation of the microsomal esterases is rate-limiting for the hydrolysis of the aliphatic esters of 3-OH-benzodiazepines.

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“…The " h2 " proteins of liver were found in the cathodic region as 5 arcs, some of which were reduced, while others were not detectable in hepatoma. (Rossowski, Weinrander and Hierowski, 1963;Deckers, 1964; Stanislawski et al, 1964;Abelev, 1965;Baldwin, 1965;Hase and Mahin, 1965;Khramkova and Guelstein, 1965;Fritz, 1966;Kashkin, 1966;Kitagawa et al, 1966;Lundkvist and Perlmann, 1966;Takayanagi, 1966;Beloshapkina and Khramkova, 1967;Dufour et al, 1967;LeBouton, 1967; Nikolaev, Li and Mil'non, 1967;Salerno, Courcon and Grabar, 1967;Schwenke and Kujawa, 1967;Chordi et al, 1969; Szafarz, Yamamoto and Weisburger, 1969;Louis and Blunck, 1970 …”

mentioning

confidence: 99%

A Comparative Study of the Proteins of Rat Plasma, Liver and Hepatoma by Agarose Immunoelectrophoresis

Deckers¹,

Glass²,

Grantham³

et al. 1972

Br J Cancer

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Summary.-A convenient and selective microtechnique, agarose immunoelectrophoresis, was applied to a comparison of the antigens in rat liver and plasma, and in primary hepatoma induced in male Fischer strain rats with N-2-fluorenylacetamide or N-hydroxy-N-2-fluorenylacetamide. Of the many soluble proteins antigenic in this system, 3 were singled out for detailed study. The albumin in liver and hepatoma had a higher mobility than that in plasma. Extraction of the soluble fraction of rat liver with ether, or treatment with absorbing charcoal, yielded an albumin band with a mobility identical to that in plasma, suggesting that liver albumin carries absorbed molecules with electronegative charges. The transferrin arc from liver, plasma and hepatoma had identical mobility. One protein with low mobility was present in higher concentration in the soluble liver fraction of male than of female rats, but it was reduced in hepatoma of male rats. The " h2 " proteins of liver were found in the cathodic region as 5 arcs, some of which were reduced, while others were not detectable in hepatoma. (Rossowski, Weinrander and Hierowski, 1963;Deckers, 1964; Stanislawski et al., 1964;Abelev, 1965;Baldwin, 1965;Hase and Mahin, 1965;Khramkova and Guelstein, 1965;Fritz, 1966;Kashkin, 1966;Kitagawa et al., 1966;Lundkvist and Perlmann, 1966;Takayanagi, 1966;Beloshapkina and Khramkova, 1967;Dufour et al., 1967;LeBouton, 1967; Nikolaev, Li and Mil'non, 1967;Salerno, Courcon and Grabar, 1967;Schwenke and Kujawa, 1967;Chordi et al., 1969; Szafarz, Yamamoto and Weisburger, 1969;Louis and Blunck, 1970

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Immunochemical Studies of Submicrosomal Membranes from Liver of Normal and Phenobarbital-Treated Rats

Cited by 19 publications

References 14 publications

Effect of Age and Comedication on Levetiracetam Pharmacokinetics and Tolerability

Effect of Age and Comedication on Levetiracetam Pharmacokinetics and Tolerability

Structural parameters in the microsomal hydrolysis of 3-acyloxy-l, 4-benzodiazepines and the multiplicity of the esterases involved

A Comparative Study of the Proteins of Rat Plasma, Liver and Hepatoma by Agarose Immunoelectrophoresis

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