A population pharmacokinetic screen to identify demographic-clinical covariates of basiliximab in liver transplantation

Kovarik, John M.; Nashan, Björn; Neuhaus, P.; Clavien, Pierre‐Alain; Gerbeau, C; Hall, Michael; Korn, Alexander

doi:10.1067/mcp.2001.114887

Cited by 45 publications

(29 citation statements)

References 13 publications

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“…The population PK analysis for trastuzumab showed a significant influence of WT on V 1 but was not considered clinically relevant . Similar results have been reported for the chimeric antibody basiliximab (Kovarik et al, 2001). The incorporation of WT on V 1 for golimumab, a fully human mAb, significantly improved the model (Zhou et al, 2007).…”

Section: Discussionsupporting

confidence: 74%

“…Beside the low peripheral volume, the intercompartmental clearance Q also indicated a limited distribution, which was consistent with the behaviour of endogenous IgG immunoglobulins (Morell et al, 1970;Koleba and Ensom, 2006;Kuester and Kloft, 2006). In total, matuzumab showed similar PK characteristics (clearance and volumes of distribution) to other therapeutic mAbs following intravenous administration (Mould et al, 1999;Kovarik et al, 2001;Bruno et al, 2005).…”

Section: Discussionmentioning

confidence: 93%

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Population pharmacokinetic data analysis of three phase I studies of matuzumab, a humanised anti-EGFR monoclonal antibody in clinical cancer development

et al. 2008

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A population pharmacokinetic model based on data from three phase I studies was to be developed including a covariate analysis to describe the concentration -time profiles of matuzumab, a novel humanised monoclonal antibody. Matuzumab was administered as multiple 1 h i.v. infusions with 11 different dosing regimens ranging from 400 to 2000 mg, q1w -q3w. For analysis, 90 patients with 1256 serum concentration -time data were simultaneously fitted using the software NONMEMt. Data were best described using a two-compartment model with the parameters central (V 1 ) and peripheral distribution volume (V 2 ), intercompartmental (Q) and linear (CLL) clearance and an additional nonlinear elimination pathway (K m , V max ). Structural parameters were in agreement with immunoglobulin characteristics. In total, interindividual variability on V max , CLL, V 1 and V 2 and interoccasion variability on CLL was 22 -62% CV. A covariate analysis identified weight having an influence on V 1 ( þ 0.44% per kg) and CLL ( þ 0.87% per kg). All parameters were estimated with good precision (RSEo39%). A robust population pharmacokinetic model for matuzumab was developed, including a nonlinear pharmacokinetic process. In addition, relevant and plausible covariates were identified and incorporated into the model. When correlated to efficacy, this model could serve as a tool to guide dose selection for this 'targeted' cancer therapy.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 93%

Population pharmacokinetic data analysis of three phase I studies of matuzumab, a humanised anti-EGFR monoclonal antibody in clinical cancer development

et al. 2008

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“…Rarely does a combined linear and non-linear process describe the elimination of antibodies (Kuester et al, 2008). Values of the final parameters were similar to those reported for other antibodies, with regard to CL from the central compartment and Q, V1 and V2 (Kovarik et al, 2001;Bruno et al, 2005;Ng et al, 2006;Dartois et al, 2007;Mould et al, 2007;Kuester et al, 2008;Lu et al, 2008). This indicates that the HuHMFG1 antibody, similar to other therapeutic antibodies, is mainly distributed in the serum.…”

Section: Discussionsupporting

confidence: 64%

“…Indeed, a structural two-compartmental model is commonly reported to describe the behaviour of antibodies. In these models, the associated elimination is mainly linear (Kovarik et al, 2001;Bruno et al, 2005;Ng et al, 2006;Dartois et al, 2007) and less frequently non-linear (Mould et al, 1999(Mould et al, , 2007. Rarely does a combined linear and non-linear process describe the elimination of antibodies (Kuester et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of the humanised monoclonal antibody, HuHMFG1 (AS1402), derived from a phase I study on breast cancer

Royer

Wu²,

Pegram

et al. 2010

Br J Cancer

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BACKGROUND: HuHMFG1 (AS1402) is a humanised monoclonal antibody that has undergone a phase I trial in metastatic breast cancer. The aim of this study was to characterise the pharmacokinetics (PKs) of HuHMFG1 using a population PK model. METHOD: Data were derived from a phase I study of 26 patients receiving HuHMFG1 at doses ranging from 1 to 16 mg kg À1 . Data were analysed using NONMEM software and covariates were included. A limited sampling strategy (LSS) was developed using training and a validation data set. RESULTS: A linear two-compartment model was shown to be adequate to describe data. Covariate analysis indicated that weight was not related to clearance. An LSS was successfully developed on the basis of the model, in which one sample is collected immediately before the start of an infusion and the second is taken at the end of infusion. CONCLUSION: A two-compartment population PK model successfully describes HuHMFG1 behaviour. The model suggests using a fixed dose of HuHMFG1, which would simplify dosing. The model could be used to optimise dose level and dosing schedule if more data on the correlation between exposure and efficacy become available from future studies. The derived LSS could optimise further PK assessment of this antibody.

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“…Basiliximab is a chimeric antibody, whereas daclizumab is a humanized antibody. Notably, basiliximab clearance correlates with the cumulative volume of ascites drained in the first week following dosing [84]. In adult liver transplant patients, the number needed to treat (NNT) to prevent one acute rejection is 15, whereas the NNT to prevent one steroid-resistant rejection is 29 [85].…”

Section: Liver Diseasementioning

confidence: 99%

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

Sofia

Rubin

2017

Dig Dis Sci

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The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

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A population pharmacokinetic screen to identify demographic-clinical covariates of basiliximab in liver transplantation

Cited by 45 publications

References 13 publications

Population pharmacokinetic data analysis of three phase I studies of matuzumab, a humanised anti-EGFR monoclonal antibody in clinical cancer development

Population pharmacokinetic data analysis of three phase I studies of matuzumab, a humanised anti-EGFR monoclonal antibody in clinical cancer development

Population pharmacokinetics of the humanised monoclonal antibody, HuHMFG1 (AS1402), derived from a phase I study on breast cancer

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

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