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Plasma protein binding of dicloxacillin: effects of age and diseases
G M Pacifici1, A Viani, G Taddeucci-Brunelli
1Department of General Pathology, Medical School, University of Pisa, Italy.
Insights
Dicloxacillin protein binding varies across different patient groups, with healthy subjects showing significantly lower unbound fractions compared to most others. Albumin concentration influences binding, similar to healthy plasma levels.
Area of Science:
- Pharmacokinetics
- Drug Metabolism
- Clinical Chemistry
Background:
- Understanding drug protein binding is crucial for optimizing therapeutic efficacy.
- Dicloxacillin is an antibiotic whose pharmacokinetic profile may be influenced by protein binding.
- Variations in protein binding can occur due to physiological and pathological conditions.
Purpose of the Study:
- To investigate dicloxacillin protein binding in various populations, including neonates, children, elderly, and patients with liver or renal impairment.
- To compare dicloxacillin unbound fractions across these diverse groups.
- To assess the role of albumin in dicloxacillin binding.
Main Methods:
- Protein binding of dicloxacillin was determined using sera and plasma from umbilical cords, children, healthy adults, elderly, and patients with liver cirrhosis or renal failure.
- Unbound fractions were quantified and statistically analyzed.
- Kinetics of dicloxacillin protein binding were studied in serum albumin and plasma samples.
Main Results:
- Healthy subjects exhibited a significantly lower unbound fraction of dicloxacillin compared to most other groups (p < 0.05).
- Patients with liver cirrhosis, renal failure, and those undergoing hemodialysis showed higher unbound fractions.
- Dicloxacillin binding in human albumin solution (45 g/l) mirrored that of healthy adult plasma.
Conclusions:
- Dicloxacillin protein binding is significantly altered in various disease states and age groups.
- Reduced protein binding in certain populations may necessitate dosage adjustments.
- Albumin concentration is a key determinant of dicloxacillin's unbound fraction.
Abstract:
Dicloxacillin protein binding was investigated in sera from 10 umbilical cords, 20 children (aged between 2 and 21 months) and in the plasma from 8 healthy young subjects, 7 healthy elderlies, 10 patients with liver cirrhosis, 10 patients with renal failure (glomerulonephritis) and 10 chronic uremics maintained on hemodialysis. The percentage unbound fraction (mean +/- SD) of dicloxacillin was 7.3 +/- 0.8 (healthy subjects), 9.8 +/- 0.6 (umbilical cords), 7.4 +/- 2.8 (children), 8.8 +/- 1.0 (elderlies), 11.8 +/- 6.3 (cirrhosis), 10.5 +/- 2.0 (renal failure), 12.7 +/- 2.0 (before hemodialysis) and 11.7 +/- 2.1 (after hemodialysis). Healthy subjects were different from all the groups (0.001 greater than p greater than 0.05) except children (p greater than 0.5) (Student's t-test). Human isolated albumin (45 g/l) bound dicloxacillin at the same degree as the plasma of healthy subjects. The kinetics of dicloxacillin protein binding was studied in three umbilical cord serum, three adult plasma specimens and in human serum albumin. The number of binding sites (n) and the association constant (k) were estimated by Lineweaver-Burk double reciprocal plot.(ABSTRACT TRUNCATED AT 250 WORDS)