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A method of calculating the PK/PD breakpoint in the sequential administration of time-dependent antibiotics
Pages: 435-440
Year: Issue:  5
Journal: Chinese Journal of Antibiotics

Abstract: Objective A new calculation method of f%T>MIC was used to calculate the PK/PD breakpoint of a time-dependent antibiotic treatment in the sequential antibiotic administration in Beagle dogs and the results were compared with multiple intravenous administrations and oral administrations.Methods Sequential administrations (3d×190mg/tid,i.v.+4d×250mg/bid,p.o.),multiple intravenous injections (7d×190mg/tid,i.v.) and multiple oral administrations (7d×250mg/bid,p.o.) were designed as three administration regimens in Beagle dogs.Based on the single administration,the C-T curve of three administration regimens according to the "superposition" principle in pharmacokinetics was obtained using simulative methodology and the f% T>MIC formula was established;PK/PD breakpoints in three regimens were calculated and evaluated by Monte Carlo models.Results The PK/PD breakpoints of the sequential administration,the intravenous injection and the oral administration in Beagle dogs were 24.1,23.6 and 7.98μg/mL,respectively.Conclusion The simulation results showed that the new calculation method of f%T>MIC could be used to calculate the PK/PD breakpoints of a time-dependent antibiotic in the sequential antibiotic administration.The sequential administration had a PK/PD breakpoint value similar to that of intravenous injections,and thus the sequential administration could be considered as the alternative regimen for multiple intravenous injections.
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