Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1984-10-12
|
| pubmed:abstractText |
Single-dose and steady-state studies were carried out in rabbits to characterize the pharmacokinetics of methicillin elimination and tissue distribution. Serum methicillin concentrations after single doses exhibited a biexponential decline with a mean terminal half-life of 27 +/- 5 min. Steady-state volume of distribution (Vdss) decreased twofold as doses increased from 5 to 125 mg/kg, while total clearance was consistent over this dosage range. During steady-state infusions of 8.7-87.2 mg/kg/h, the serum and extravascular fluid concentrations increased in proportion to dose, while clearance remained constant. Methicillin tissue concentrations did not increase in proportion to dose and serum concentration, and the Vdss measured from tissue recovery decreased as dosage and serum concentrations increased. Central compartment volume and serum protein binding did not change. The cause of the dose-dependent change in Vdss was a capacity-limited uptake of methicillin into essentially all nonexcretory tissues. This process was described by a partial physiological pharmacokinetic model based on the actual weights or volumes of the rabbit tissues. Distribution into extracellular fluids was assumed to be complete, while entry into cellular, nonexcretory tissue became capacity limited as the Km (17.2 micrograms/mL) was exceeded. The result was a decline in Vdss with increasing serum concentrations to a limiting value which approached the volume of the central space (Vc) and was similar to the extracellular water volume of the rabbit (0.17 L/kg). In the dosage range where total clearance was independent of serum concentration, the distribution of methicillin was concentration dependent and could be predicted by equations derived from the Michaelis-Menten equation.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0022-3549
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
73
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
867-73
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:6470946-Animals,
pubmed-meshheading:6470946-Half-Life,
pubmed-meshheading:6470946-Infusions, Parenteral,
pubmed-meshheading:6470946-Injections, Intravenous,
pubmed-meshheading:6470946-Kinetics,
pubmed-meshheading:6470946-Methicillin,
pubmed-meshheading:6470946-Rabbits,
pubmed-meshheading:6470946-Tissue Distribution
|
| pubmed:year |
1984
|
| pubmed:articleTitle |
Pharmacokinetics of capacity-limited tissue distribution of methicillin in rabbits.
|
| pubmed:publicationType |
Journal Article
|