Comparative Drug Metabolism

Mellett, L. B.

doi:10.1007/978-3-0348-7068-9_3

Cited by 27 publications

(12 citation statements)

References 44 publications

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“…Considering the interval (2 h) between anticancer drug administration and DDTC injection and plasma clearance half-times of DX (Formelli et al, 1985), CY (Mellet, 1969) and cis-DDP (Brock & Pohl, 1983;Evans et al, 1984) in mice, the antitumour drugs probably reach target sites before DDTC administration. Thus the latter possibly operates interfering with the anticancer drug action at a cellular level.…”

Section: Discussionmentioning

confidence: 99%

Effect of diethyldithiocarbamate on toxicity of doxorubicin, cyclophosphamide and cis-diamminedichloroplatinum (II) on mice haemopoietic progenitor cells

Pannacciulli

Lerza²,

Bogliolo³

et al. 1989

Br J Cancer

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Section: Discussionmentioning

confidence: 99%

Effect of diethyldithiocarbamate on toxicity of doxorubicin, cyclophosphamide and cis-diamminedichloroplatinum (II) on mice haemopoietic progenitor cells

Pannacciulli

Lerza²,

Bogliolo³

et al. 1989

Br J Cancer

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“…The doses of ticarcillin and clavulanic acid used in the experiments reported here approximated, in terms of body surface area, a dose in humans of 3 g of ticarcillin with 100 mg of clavulanic acid. Body surface area is a function of body weight to the two-thirds power (6,11), and its use in adjusting doses may be regarded as a means to allow for species differences in physiology and metabolism. The influence of body size on pharmacokinetics is through its correlation with blood flow and clearance (12), and pharmacokinetic parameters for a number of compounds including ,B-lactam antibiotics have been shown to correlate with body size (either body surface area or body weight) for a wide range of mammalian species including humans (4,6,11,17).…”

Section: Discussionmentioning

confidence: 99%

“…Body surface area is a function of body weight to the two-thirds power (6,11), and its use in adjusting doses may be regarded as a means to allow for species differences in physiology and metabolism. The influence of body size on pharmacokinetics is through its correlation with blood flow and clearance (12), and pharmacokinetic parameters for a number of compounds including ,B-lactam antibiotics have been shown to correlate with body size (either body surface area or body weight) for a wide range of mammalian species including humans (4,6,11,17). By definition, the AUC is solely a function of clearance, and it is therefore of interest that the AUCs for ticarcillin and clavulanic acid in rat and rabbit sera approximated those observed in humans after a dose of 3 g of ticarcillin with 100 mg of clavulanic acid.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics and distribution of ticarcillin-clavulanic acid (Timentin) in experimental animals

Woodnutt

Kernutt

Mizen

1987

Antimicrob Agents Chemother

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The pharmacokinetics and distribution of ticarcillin and clavulanic acid were studied in rats and rabbits after intravenous coadministration of the compounds. The elimination half-lives for ticarcillin and clavulanic acid were similar in both rats (ticarcillin, 0.22 h; clavulanic acid, 0.24 h) and rabbits (ticarcillin, 0.38 h; clavulanic acid, 0.31 h). Both compounds distributed widely throughout rat tissues, and the patterns of distribution were similar to those observed for other j3-lactams. Values for penetration into rat pleural, peritoneal, and subcutaneous fluids calculated from the equation (AUCfljd/AUC,.rum) x 100, where AUC is the area under the concentration-time curve, were between 83 and 93% for ticarcillin and 86 and 103% for clavulanic acid. Values for penetration into tissue cages in rabbits were 139% 45% for ticarcillin and 109% + 22% for clavulanic acid. The penetration of clavulanic acid into rabbit cerebrospinal fluid was higher (P < 0.05) (4.0% 0.61%) than that of ticarcillin (1.3% ± 0.53%). Overall, the results show that ticarcillin and clavulanic acid distribute readily throughout body tissues and fluids and predict that the penicillin and ,-lactamase inhibitor would be present together at sites of infection.Ticarcillin is active against a broad range of gram-positive and -negative bacteria, including Pseudomonas aeruginosa. It shows moderate stability in the presence of the Richmond class I ,-lactamases but is inactivated by most other ,Blactamases encountered in clinical isolates. In the presence of the ,B-lactamase inhibitor clavulanic acid, however, the spectrum of activity is extended to include many bacterial strains resistant to ticarcillin alone (5,7,15).In the treatment of infections, the inhibitor should display distribution characteristics similar to ticarcillin to achieve effective concentrations of both compounds at infected sites. In the experiments described here, the pharmacokinetics and distribution properties of ticarcillin and clavulanic acid were characterized after intravenous coadministration of the two compounds to rats and rabbits. The doses administered in the experiments were calculated on the basis of dose/ surface area (11) to be comparable with a recommended dose of ticarcillin-clavulanic acid for humans (3 g of ticarcillin with 100 mg of clavulanic acid; 3.1 g of Timentin [Beecham Pharmaceuticals, Worthing, England] The blood samples removed from the rats at 5, 45, and 90 min and from the rabbits at 10 and 60 min were used for determination of the binding of ticarcillin and clavulanic acid to serum proteins. Portions of the samples were kept for bioassay, and the remaining volumes of sera were centrifuged through a Centrifree micropartition system (Amicon, Gloucestershire, England)

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“…The capacity of the liver microsomal enzymes to metabolize drugs undergoes substantial changes with ad vancing age (Çonney, 1967;Fours, 1971;Geokas and Haverback, 1969). It has been shown that there is greater drug-metabolizing enzyme activity in young than in old rats (Baird et ai, 1976;Kato et a i, 1964;Kato and Ta ka naka, 1968;Mellett, 1969). However, these changes would also seem to vary with the sub strate used (Slanina and Stalhandske, 1977).…”

mentioning

confidence: 92%

Fine Structural Changes in the Liver of Young and Old Rats as Influenced by Microsomal Enzyme Inducers

Garg¹,

Kourounakis²,

Tuchweber³

1979

Gerontology

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When given orally to young and old rats, pregnenolone-16α-carbonitrile, spironolactone, or phenobarbital, known microsomal enzyme inducers, caused an increase in smooth endoplasmic reticulum. Dexamethasone, while a potent microsomal enzyme inducer, did not cause smooth endoplasmic reticulum increase. In both untreated and treated old rats, there was dilatation and vesiculation of rough endoplasmic reticulum with occasional granular material present in vesicles. Cytoplasmic lipid droplets of various sizes were frequent. Some mitochondria exhibited polymorphism and a variation in matrical density. Lysosomes and autophagic vacuoles as well as lipid droplets of various sizes were frequent in all groups. These results show that microsomal enzyme inducers influence the subcellular structure of hepatocytes in old rats.

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Comparative Drug Metabolism

Cited by 27 publications

References 44 publications

Effect of diethyldithiocarbamate on toxicity of doxorubicin, cyclophosphamide and cis-diamminedichloroplatinum (II) on mice haemopoietic progenitor cells

Effect of diethyldithiocarbamate on toxicity of doxorubicin, cyclophosphamide and cis-diamminedichloroplatinum (II) on mice haemopoietic progenitor cells

Pharmacokinetics and distribution of ticarcillin-clavulanic acid (Timentin) in experimental animals

Fine Structural Changes in the Liver of Young and Old Rats as Influenced by Microsomal Enzyme Inducers

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