From e29419f7eea47228d575e4f10afa1a2fa21f8be9 Mon Sep 17 00:00:00 2001 From: Jordan Brooks Date: Fri, 31 Oct 2025 19:59:58 +0000 Subject: [PATCH 1/2] RXR-2747: add tgtmic-containing model to inst --- inst/models/pk_cefepime_an.json5 | 135 +++++++++++++++++++++++++++++++ 1 file changed, 135 insertions(+) create mode 100644 inst/models/pk_cefepime_an.json5 diff --git a/inst/models/pk_cefepime_an.json5 b/inst/models/pk_cefepime_an.json5 new file mode 100644 index 0000000..f9f5f30 --- /dev/null +++ b/inst/models/pk_cefepime_an.json5 @@ -0,0 +1,135 @@ +{ + "id": "pk_cefepime_an", + "description": "PK model for cefepime in critically ill adults", + "drug": "cefepime", + "category": "antibacterial", + "age_categories": [ "adults" ], + "subpopulations": [ "critically_ill" ], + "equations": [ + 'CL_i = CL_{r,nonCRRT} * \\frac{CLCR_{LBW}}{54} + CL_{nr}', + 'V_{1,i} = V_{1,base} * (WT/90)', + 'Q_i = Q_{base}', + 'V_{2,i} = V_{2,base}', + '\\frac{dA_1}{dt} = -(CL_i/V_i) * A_1 - (Q_i/V_i) * A_1 + (Q_i/V_{2,i}) * A_2', + '\\frac{dA_2}{dt} = (Q_i/V_i) * A_1 - (Q_i/V_{2,i}) * A_2' + ], + "ode_code": "\ + dAdt[0] = -(CLtot/Vi)*A[0] - (Qi/Vi)*A[0] + (Qi/V2i)*A[1];\ + dAdt[1] = +(Qi/Vi)*A[0] - (Qi/V2i)*A[1];\ + CONC = A[0]/Vi \ + CONCF = CONC * FU \ + dAdt[2] = (CONC>MIC) \ + dAdt[3] = (CONC > (4 * MIC)) \ + dAdt[4] = (CONCF>MIC) \ + dAdt[5] = (CONCF > (4 * MIC)) \ + dAdt[6] = CONC \ + TGTMIC = A[2] \ + TGT4MIC = A[3] \ + FTGTMIC = A[4] \ + FTGT4MIC = A[5] \ + ", + "pk_code": "\ + if (SEX == 1) { \ + LBW = 1.1 * WT - 0.0128 * pow(WT, 2) / pow(HT, 2) \ + } else { \ + LBW = 1.07 * WT - 0.0148 * pow(WT, 2) / pow(HT, 2) \ + } \ + LBW = max(LBW, 30.0) \ + CRCLi = (140.0 - AGE) * LBW * pow(0.85, (1.0-SEX)) / (72.0 * CR) \ + // if (CRRT > 0) { \ + // CLr = 1.64 \ + // } else { \ + CLr = 2.00 * (CRCLi / 54.0) \ + // } \ + CLtot = CLiiv * (CLr + CLnr) + CL_HEMO \ + Vi = V * (WT/90.0) \ + Qi = Q \ + V2i = V2 \ + ", + "n_comp": 7, + "obs": { "cmt": 1, "variable": ["CONC"] }, + "dose": { "cmt": 1, "bioav": [1] }, + "cmt_mapping": { + "infusion": 1, + "infusion_iiv": 1, + "infusion_civ": 1 + }, + "covariates": [ "WT", "CR", "CL_HEMO", "MIC", "SEX", "AGE", "HT", "FU" ], + "variables": [ "Vi", "Qi", "V2i", "CRCLi", "LBW", "CLtot", "TGTMIC", "TGT4MIC", "FTGTMIC", "FTGT4MIC", "CLr", "CONC", "CONCF" ], + "parameters" : { + "CLiiv": 1, + "V": 13.4, + "Q": 12.0, + "V2": 7.52, + "CLnr": 0.526 + }, + "fixed": [ + "Q", + "CLnr" + ], + "units": { + "CL": "L/hr", + "V": "L/kg", + "Vi": "L", + "Q": "L/hr", + "V2": "L" + }, + "iiv": { + "CL": 0.299, + "V": 0.654, + "V2": 0.173 + }, + "omega_matrix": [ + 0.089401, + 0, 0.427716, + 0, 0, 0.029929 + ], + "ruv": { + "prop": [0.224], + "add": [6.44] + }, + "misc": { + "model_type": "2cmt_iv", + "linearity": "linear", + "timevarying_parameter": false, + "init_parameter": true + }, + "development": { + "n_patients": 130, + "n_tdms": 278, + "age": { "median": 65, "IQR25": 52, "IQR75": 72, "unit": "years" }, + "weight": { "median": 90, "IQR25": 70, "IQR75": 110, "unit": "kg" }, + "crcl": { "median": 86, "IQR25": 52, "IQR75": 126, "unit": "ml/min" }, + "sex": { "male": 76, "female": 54 } + }, + "references": [ + { + "ref": "Guohua An, et al., 2023", + "url": "https://academic.oup.com/jac/article-abstract/78/6/1460/7127727" + } + ], + "active": true, + "build": true, + "admin": [ + { + "implementer": { "name": "Jasmine Hughes", "email": "jasmine@insight-rx.com" }, + "format": "PKPDsim" + }, + { + "implementer": { "name": "Jordan Brooks", "email": "jordan.brooks@insight-rx.com" }, + "format": "NONMEM" + } + ], + "implementations": { + "nonmem": "pk_cefepime_an.mod" + }, + "comments": [ + "Assumes Green method for determining LBW." + ], + "validation": { + "implementation": true, + "numerical": true, + "clinical": false + }, + "version": "0.1.8" +} From e4704cca1a46da8ad56aa4c098d4f0670b655852 Mon Sep 17 00:00:00 2001 From: Jordan Brooks Date: Thu, 20 Nov 2025 17:47:09 +0000 Subject: [PATCH 2/2] remove metadata fields --- inst/models/pk_cefepime_an.json5 | 45 +------------------------------- 1 file changed, 1 insertion(+), 44 deletions(-) diff --git a/inst/models/pk_cefepime_an.json5 b/inst/models/pk_cefepime_an.json5 index f9f5f30..2748502 100644 --- a/inst/models/pk_cefepime_an.json5 +++ b/inst/models/pk_cefepime_an.json5 @@ -1,18 +1,5 @@ { "id": "pk_cefepime_an", - "description": "PK model for cefepime in critically ill adults", - "drug": "cefepime", - "category": "antibacterial", - "age_categories": [ "adults" ], - "subpopulations": [ "critically_ill" ], - "equations": [ - 'CL_i = CL_{r,nonCRRT} * \\frac{CLCR_{LBW}}{54} + CL_{nr}', - 'V_{1,i} = V_{1,base} * (WT/90)', - 'Q_i = Q_{base}', - 'V_{2,i} = V_{2,base}', - '\\frac{dA_1}{dt} = -(CL_i/V_i) * A_1 - (Q_i/V_i) * A_1 + (Q_i/V_{2,i}) * A_2', - '\\frac{dA_2}{dt} = (Q_i/V_i) * A_1 - (Q_i/V_{2,i}) * A_2' - ], "ode_code": "\ dAdt[0] = -(CLtot/Vi)*A[0] - (Qi/Vi)*A[0] + (Qi/V2i)*A[1];\ dAdt[1] = +(Qi/Vi)*A[0] - (Qi/V2i)*A[1];\ @@ -49,7 +36,7 @@ "n_comp": 7, "obs": { "cmt": 1, "variable": ["CONC"] }, "dose": { "cmt": 1, "bioav": [1] }, - "cmt_mapping": { + "cmt_mapping": { "infusion": 1, "infusion_iiv": 1, "infusion_civ": 1 @@ -67,13 +54,6 @@ "Q", "CLnr" ], - "units": { - "CL": "L/hr", - "V": "L/kg", - "Vi": "L", - "Q": "L/hr", - "V2": "L" - }, "iiv": { "CL": 0.299, "V": 0.654, @@ -108,28 +88,5 @@ "url": "https://academic.oup.com/jac/article-abstract/78/6/1460/7127727" } ], - "active": true, - "build": true, - "admin": [ - { - "implementer": { "name": "Jasmine Hughes", "email": "jasmine@insight-rx.com" }, - "format": "PKPDsim" - }, - { - "implementer": { "name": "Jordan Brooks", "email": "jordan.brooks@insight-rx.com" }, - "format": "NONMEM" - } - ], - "implementations": { - "nonmem": "pk_cefepime_an.mod" - }, - "comments": [ - "Assumes Green method for determining LBW." - ], - "validation": { - "implementation": true, - "numerical": true, - "clinical": false - }, "version": "0.1.8" }