Population pharmacokinetic evaluation and optimization of amikacin dosage regimens for the management of mycobacterial infections
| Autor: | Alison H. Thomson, Hinke Siebinga, Fiona Robb |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.medical_specialty RM 030106 microbiology Population Cmax Gastroenterology 03 medical and health sciences Cmin 0302 clinical medicine Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) 030212 general & internal medicine Dosing education Amikacin Pharmacology education.field_of_study medicine.diagnostic_test business.industry Anti-Bacterial Agents NONMEM Infectious Diseases Therapeutic drug monitoring business Monte Carlo Method medicine.drug |
| ISSN: | 0305-7453 |
| Popis: | Background There is limited information on amikacin pharmacokinetics (PK) and dose requirements in patients with mycobacterial infections. Objectives To conduct a population PK analysis of amikacin data from patients with mycobacterial infections and compare predicted concentrations from standard and modified dosage guidelines with recommended target ranges. Methods A population PK model was developed using NONMEM. Cmax, Cmin, concentration 1 h post-infusion (C1h) and AUC0–24 using 15 mg/kg daily (once daily), the WHO table, 25 mg/kg three times weekly (TTW) and modified guidelines were compared using Monte Carlo simulations of 1000 patients. Results Data were available from 124 patients (684 concentrations) aged 16–92 years. CL was 4.64 L/h per 100 mL/min CLCR; V was 0.344 L/kg. With once-daily regimens, Cmax was 35–45 mg/L in 30%–35% of patients and 35–50 mg/L in 46%–48%; C1h was 25–40 mg/L in 53%–59%. The WHO table produced high Cmax values in patients 75 kg. With TTW dosing, around 30% of Cmax values were 65–80 mg/L, 40% were 60–80 mg/L, and 48% of C1h were 45–65 mg/L. Increasing the dosage interval for patients with CLCR 2 mg/L from 34% to 25% for once-daily dosing and from 18% to 13% for TTW. In patients whose Cmin was Conclusions Standard amikacin dosing guidelines achieve low percentages of target concentrations for mycobacterial infections. Extending the dosing interval in renal impairment and widening target ranges would reduce the need for dose adjustment. |
| Databáze: | OpenAIRE |
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