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Evaluating darunavi...
Evaluating darunavir/ritonavir dosing regimens for HIV-positive pregnant women using semi-mechanistic pharmacokinetic modelling
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- Schalkwijk, Stein (författare)
- Radboud Univ Nijmegen, RIHS, Dept Pharm, Med Ctr, Nijmegen, Netherlands;Radboud Univ Nijmegen, Dept Pharmacol & Toxicol, RIMLS, Med Ctr, Nijmegen, Netherlands
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- ter Heine, Rob (författare)
- Radboud Univ Nijmegen, RIHS, Dept Pharm, Med Ctr, Nijmegen, Netherlands
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- Colbers, Angela (författare)
- Radboud Univ Nijmegen, RIHS, Dept Pharm, Med Ctr, Nijmegen, Netherlands
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- Capparelli, Edmund (författare)
- Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA;Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA
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- Best, Brookie M. (författare)
- Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA;Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA
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- Cressey, Tim R. (författare)
- Chiang Mai Univ, Fac Associated Med Sci, Chiang Mai, Thailand;Harvard TH Chan Sch Publ Hlth, Boston, MA USA;Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England
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- Greupink, Rick (författare)
- Radboud Univ Nijmegen, Dept Pharmacol & Toxicol, RIMLS, Med Ctr, Nijmegen, Netherlands
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- Russel, Frans G. M. (författare)
- Radboud Univ Nijmegen, Dept Pharmacol & Toxicol, RIMLS, Med Ctr, Nijmegen, Netherlands
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- Molto, Jose (författare)
- Hosp Badalona Germans Trias & Pujol, Fundacio Lluita Sida, Badalona, Spain;Hosp Badalona Germans Trias & Pujol, Infect Dis Dept, Badalona, Spain;Univ Autonoma Barcelona, Barcelona, Spain
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- Mirochnick, Mark (författare)
- Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA
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- Karlsson, Mats (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Burger, David M. (författare)
- Radboud Univ Nijmegen, RIHS, Dept Pharm, Med Ctr, Nijmegen, Netherlands
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(creator_code:org_t)
- 2019-01-30
- 2019
- Engelska.
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Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 74:5, s. 1348-1356
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Background: Darunavir 800mg once (q24h) or 600 mg twice (q12h) daily combined with low-dose ritonavir is used to treat HIV-positive pregnant women. Decreased total darunavir exposure (17%-50%) has been reported during pregnancy, but limited data on unbound exposure are available. Objectives: To evaluate total and unbound darunavir exposures following standard darunavir/ritonavir dosing and to explore the value of potential optimized darunavir/ritonavir dosing regimens for HIV-positive pregnant women. Patients and methods: A population pharmacokinetic analysis was conducted based on data from 85 women. The final model was used to simulate total and unbound darunavir AUC(0-tau) and C-trough during the third trimester of pregnancy, as well as to assess the probability of therapeutic exposure. Results: Simulations predicted that total darunavir exposure (AUC(0-tau)) was 24% and 23% lower in pregnancy for standard q24h and q12h dosing, respectively. Unbound darunavir AUC(0-tau) was 5% and 8% lower compared with post-partum for standard q24h and q12h dosing, respectively. The probability of therapeutic exposure (unbound) during pregnancy was higher for standard q12h dosing (99%) than for q24h dosing (94%). Conclusions: The standard q12h regimen resulted in maximal and higher rates of therapeutic exposure compared with standard q24h dosing. Darunavir/ritonavir 600/100 mg q12h should therefore be the preferred regimen during pregnancy unless (adherence) issues dictate q24h dosing. The value of alternative dosing regimens seems limited.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
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Schalkwijk, Stei ...
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ter Heine, Rob
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Colbers, Angela
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Capparelli, Edmu ...
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Best, Brookie M.
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Cressey, Tim R.
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visa fler...
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Greupink, Rick
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Russel, Frans G. ...
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Molto, Jose
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Mirochnick, Mark
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Karlsson, Mats
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Burger, David M.
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