Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in Pakistan
Background: Vancomycin is a narrow therapeutic agent, and it is necessary to optimize the dose to achieve safe therapeutic outcomes. The purpose of this study was to identify the significant covariates for vancomycin clearance and to optimize the dose among surgical patients in Pakistan.Methods: Pla...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.721819/full |
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| author | Muhammad Muaaz Munir Huma Rasheed Muhammad Imran Khokhar Rizwan Rasul Khan Hafiz Asad Saeed Mateen Abbas Mohsin Ali Rabiea Bilal Hafiz Awais Nawaz Abdul Muqeet Khan Shaista Qamar Syed Muneeb Anjum Muhammad Usman |
| author_facet | Muhammad Muaaz Munir Huma Rasheed Muhammad Imran Khokhar Rizwan Rasul Khan Hafiz Asad Saeed Mateen Abbas Mohsin Ali Rabiea Bilal Hafiz Awais Nawaz Abdul Muqeet Khan Shaista Qamar Syed Muneeb Anjum Muhammad Usman |
| author_sort | Muhammad Muaaz Munir |
| collection | DOAJ |
| description | Background: Vancomycin is a narrow therapeutic agent, and it is necessary to optimize the dose to achieve safe therapeutic outcomes. The purpose of this study was to identify the significant covariates for vancomycin clearance and to optimize the dose among surgical patients in Pakistan.Methods: Plasma concentration data of 176 samples collected from 58 surgical patients treated with vancomycin were used in this study. A population pharmacokinetic model was developed on NONMEM® using plasma concentration–time data. The effect of all available covariates was evaluated on the pharmacokinetic parameters of vancomycin by stepwise covariate modeling. The final model was evaluated using bootstrap, goodness-of-fit plots, and visual predictive checks.Results: The pharmacokinetics of vancomycin followed a one-compartment model with first-order elimination. The vancomycin clearance (CL) and volume of distribution (Vd) were 2.45 L/h and 22.6 l, respectively. Vancomycin CL was influenced by creatinine clearance (CRCL) and body weight of the patients; however, no covariate was significant for its effect on the volume of distribution. Dose tailoring was performed by simulating dosage regimens at a steady state based on the CRCL of the patients. The tailored doses were 400, 600, 800, and 1,000 mg for patients with a CRCL of 20, 60, 100, and 140 ml/min, respectively.Conclusion: Vancomycin CL is influenced by CRCL and body weight of the patient. This model can be helpful for the dose tailoring of vancomycin based on renal status in Pakistani patients. |
| first_indexed | 2024-12-20T23:33:53Z |
| format | Article |
| id | doaj.art-1658c40d6d364ed0938d23558238cad3 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T23:33:53Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-1658c40d6d364ed0938d23558238cad32022-12-21T19:23:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-11-011210.3389/fphar.2021.721819721819Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in PakistanMuhammad Muaaz Munir0Huma Rasheed1Muhammad Imran Khokhar2Rizwan Rasul Khan3Hafiz Asad Saeed4Mateen Abbas5Mohsin Ali6Rabiea Bilal7Hafiz Awais Nawaz8Abdul Muqeet Khan9Shaista Qamar10Syed Muneeb Anjum11Muhammad Usman12Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, PakistanInstitute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, PakistanAmeer-ud-Din Medical College, Post-Graduate Medical Institute (PGMI), Lahore General Hospital, Lahore, PakistanDepartment of Medicine, Aziz Fatima Medical and Dental College, Faisalabad, PakistanPak Emirates Military Hospital, Rawalpindi, PakistanQuality Operation Laboratory, University of Veterinary and Animal Sciences, Lahore, PakistanDepartment of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Govt College University, Faisalabad, PakistanCMH Lahore Medical College and IOD, NUMS, Lahore, PakistanInstitute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, PakistanQuality Operation Laboratory, University of Veterinary and Animal Sciences, Lahore, PakistanInstitute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, PakistanInstitute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, PakistanInstitute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, PakistanBackground: Vancomycin is a narrow therapeutic agent, and it is necessary to optimize the dose to achieve safe therapeutic outcomes. The purpose of this study was to identify the significant covariates for vancomycin clearance and to optimize the dose among surgical patients in Pakistan.Methods: Plasma concentration data of 176 samples collected from 58 surgical patients treated with vancomycin were used in this study. A population pharmacokinetic model was developed on NONMEM® using plasma concentration–time data. The effect of all available covariates was evaluated on the pharmacokinetic parameters of vancomycin by stepwise covariate modeling. The final model was evaluated using bootstrap, goodness-of-fit plots, and visual predictive checks.Results: The pharmacokinetics of vancomycin followed a one-compartment model with first-order elimination. The vancomycin clearance (CL) and volume of distribution (Vd) were 2.45 L/h and 22.6 l, respectively. Vancomycin CL was influenced by creatinine clearance (CRCL) and body weight of the patients; however, no covariate was significant for its effect on the volume of distribution. Dose tailoring was performed by simulating dosage regimens at a steady state based on the CRCL of the patients. The tailored doses were 400, 600, 800, and 1,000 mg for patients with a CRCL of 20, 60, 100, and 140 ml/min, respectively.Conclusion: Vancomycin CL is influenced by CRCL and body weight of the patient. This model can be helpful for the dose tailoring of vancomycin based on renal status in Pakistani patients.https://www.frontiersin.org/articles/10.3389/fphar.2021.721819/fullvancomycinpopulation pharmacokineticsPakistanNONMEMdose tailoring |
| spellingShingle | Muhammad Muaaz Munir Huma Rasheed Muhammad Imran Khokhar Rizwan Rasul Khan Hafiz Asad Saeed Mateen Abbas Mohsin Ali Rabiea Bilal Hafiz Awais Nawaz Abdul Muqeet Khan Shaista Qamar Syed Muneeb Anjum Muhammad Usman Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in Pakistan Frontiers in Pharmacology vancomycin population pharmacokinetics Pakistan NONMEM dose tailoring |
| title | Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in Pakistan |
| title_full | Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in Pakistan |
| title_fullStr | Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in Pakistan |
| title_full_unstemmed | Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in Pakistan |
| title_short | Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in Pakistan |
| title_sort | dose tailoring of vancomycin through population pharmacokinetic modeling among surgical patients in pakistan |
| topic | vancomycin population pharmacokinetics Pakistan NONMEM dose tailoring |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.721819/full |
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