{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:03Z","timestamp":1787013903509,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,8,14]],"date-time":"2022-08-14T00:00:00Z","timestamp":1660435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cabotegravir delivered as a long\u2010acting intramuscular injection has shown superior efficacy to oral tenofovir\u2010emtricitabine as pre\u2010exposure prophylaxis (PrEP) for HIV. Cabotegravir pharmacokinetics (PK), like those of other long\u2010acting depot preparations, exhibit variability between individuals and between injection occasions. The aim of this study is to describe the population pharmacokinetics of long\u2010acting cabotegravir (CAB\u2010LA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using available PK measurements from 133 participants in the HIV Prevention Trials Network (HPTN) 077 trial, we analysed CAB\u2010LA PK data using nonlinear mixed\u2010effects modelling to develop a population PK model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A two\u2010compartment model with first order absorption best described the CAB\u2010LA PK. The analysis identified between\u2010occasion variability (BOV, i.e., differences in PK within one individual from one injection to the next) as a significant covariate affecting the absorption rate, with an estimated contribution of BOV to PK variability on the absorption rate (k\n                      <jats:sub>a<\/jats:sub>\n                      ) of 38.5%. Sex and body weight were identified as significant covariates influencing the absorption rate and apparent clearance of CAB\u2010LA after intramuscular injection at various doses and frequencies. Male participants had 67% higher k\n                      <jats:sub>a<\/jats:sub>\n                      than female participants. Serially adding to the model body weight on clearance, sex on k\n                      <jats:sub>a<\/jats:sub>\n                      , and BOV on k\n                      <jats:sub>a<\/jats:sub>\n                      led to a decrease in the objective function value (OFV) of 24.4, 36 and 321.4, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The public availability of this model will facilitate and enable a wide variety of future clinically relevant simulations to inform the optimal use of CAB\u2010LA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.15477","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:09:25Z","timestamp":1660176565000},"page":"4623-4632","source":"Crossref","is-referenced-by-count":12,"title":["A population pharmacokinetic model based on HPTN 077 of long\u2010acting injectable cabotegravir for HIV PrEP"],"prefix":"10.1111","volume":"88","author":[{"given":"Yifan","family":"Yu","sequence":"first","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences State University of New York at Buffalo  Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin L.","family":"Bigos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Clinical Pharmacology The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Psychiatry The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Pharmacology and Molecular Sciences The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-8786","authenticated-orcid":false,"given":"Mark 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W.","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Clinical Pharmacology The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Pharmacology and Molecular Sciences The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Medicine, Division of Infectious Diseases The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Bies","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences State University of New York at Buffalo  Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9519-3348","authenticated-orcid":false,"given":"Ethel D.","family":"Weld","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Clinical Pharmacology The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Pharmacology and Molecular Sciences The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Medicine, Division of Infectious Diseases The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the HPTN 077 Study 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Chiu J Lovern M et al.Population PK approach to predict cabotegravir (CAB GSK1265744) long\u2010acting injectable doses for phase 2b (Ph2b). 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