Voriconazole » CFR » Cmin/MIC

Source: R/simulate_voriconazole_mc_cfr_cmin_mic_ratio.R

Voriconazole » Cumulative Fraction of Response » Total minimum concentration to MIC ratio

simulate_voriconazole_mc_cfr_cmin_mic_ratio(
  PATID,
  AGE,
  HEIGHT,
  WEIGHT,
  GENDER,
  MODEL,
  RIFAMPICIN,
  SEVEREHEPATICCHOLESTASIS,
  CMINPERMIC,
  ORALORIVORKGREGIMENS,
  MICDISTR
)

Arguments

PATID

Patient Identifier. User-provided free text (such as patient id, name or alias) to identify related simulations. Must be provided as string.
AGE

Age. Age of the patient in years. Must be provided as numeric (min. 18, max. 120 year).
HEIGHT

Height. Height of the patient. Must be provided as numeric (min. 100, max. 250 cm).
WEIGHT

Weight. Actual body weight of the patient. Must be provided as numeric (min. 20, max. 500 kg).
GENDER

Sex. Patient's sex for clinical decision-making. Must be provided as string ('Male' or 'Female').
MODEL

Model for population of interest. Pharmacokinetic model to be used for specific patient type during simulations. Must be provided as string ('Pascual et al. (2012) - patients with invasive fungal infections').
RIFAMPICIN

Concurrent rifampicin. Presence of rifampicin coadministration. Must be provided as string ('No' or 'Yes').
SEVEREHEPATICCHOLESTASIS

Severe hepatic cholestasis. Severe hepatic cholestasis is defined as any liver function tests > 20 times the upper limit of normal (e.g. alkaline phosphatase, AST, ALT or GGT). Must be provided as string ('No' or 'Yes').
CMINPERMIC

Minimum concentration to MIC ratio target. The PK/PD target can be provided as minimum concentration to minimum inhibitory concentration ratio (Cmin/MIC). Must be provided as numeric (min. 0.1, max. 50 ).
ORALORIVORKGREGIMENS

Dosing Regimens. List of dosing regimens to be used in simulating target attainment, from which the dosing regimen with the smallest absolute difference from the desired target will be automatically selected. Must be provided as list of 1-8 'KGREGIMEN', 'REGIMEN' or 'ORALREGIMEN' values. Use the regimen helper function to define the REGIMEN values.
MICDISTR

MIC distribution. Non-cumulative MIC distribution of organism for the given antibiotic at the specified MICs provided as percentages with a sum of 100%. MIC distribution of voriconazole when tested against Aspergillus fumigatus. [Borman et al. "MIC Distributions and Evaluation of Fungicidal Activity for Amphotericin B, Itraconazole, Voriconazole, Posaconazole and Caspofungin and 20 Species of Pathogenic Filamentous Fungi Determined Using the CLSI Broth Microdilution Method." Journal of fungi (Basel, Switzerland) vol. 3,2 27. 31 May. 2017, doi:10.3390/jof3020027]. Must be provided as set.

Details

Drug: Voriconazole

Method: Monte Carlo simulation on the proportion of the population achieving a certain pharmacodynamic index value, given the minimum inhibitory concentration (MIC) distribution of the target microorganism(s).

PK/PD target: Minimum concentration (mg/L) to minimum inhibitory concentration ratio (mg/L).

References

  • Pascual, Andres et al. (2012): Challenging recommended oral and intravenous voriconazole doses for improved efficacy and safety: population pharmacokinetics-based analysis of adult patients with invasive fungal infections. In. Clinical Infectious Diseases. https://pubmed.ncbi.nlm.nih.gov/22610925

Examples

if (FALSE) {
simulate_voriconazole_mc_cfr_cmin_mic_ratio(PATID = "Anonymous", 
    AGE = 35, HEIGHT = 155, 
    WEIGHT = 55, GENDER = "Female", 
    MODEL = "Pascual et al. (2012) - patients with invasive fungal infections", 
    RIFAMPICIN = "No", 
    SEVEREHEPATICCHOLESTASIS = "No", 
    CMINPERMIC = 3, ORALORIVORKGREGIMENS = list(
        list(set = "REGIMEN", 
            DOSE = 200, 
            INTERVAL = 12, 
            TINF = 1.5), 
        list(set = "ORALREGIMEN", 
            DOSE = 200, 
            INTERVAL = 12)), 
    MICDISTR = list("MICDISTR-0.0625" = list(
        0.6), "MICDISTR-0.125" = list(
        13), "MICDISTR-0.25" = list(
        68.4), "MICDISTR-0.5" = list(
        12.5), "MICDISTR-1" = list(
        2.8), "MICDISTR-2" = list(
        1.9), "MICDISTR-4" = list(
        0.8)))
}