Population Pharmacokinetics of Cabotegravir Following Oral Administration and Long-Acting Intramuscular Injection in Real-World People with HIV.
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
22 Mar 2024
22 Mar 2024
Historique:
received:
18
12
2023
accepted:
25
02
2024
medline:
23
3
2024
pubmed:
23
3
2024
entrez:
23
3
2024
Statut:
aheadofprint
Résumé
Long-acting cabotegravir has been studied mainly in the stringent framework of clinical trials, which does not necessarily reflect the situation of people with HIV (PWH) in routine clinical settings. The present population pharmacokinetic analysis aims to build real-world reference percentile curves of cabotegravir concentrations, accounting for patient-related factors that may affect cabotegravir exposure. The second objective is to simulate whether dosing interval adjustments of cabotegravir could be considered in specific subpopulations. Overall, 238 PWH contributed to 1,038 cabotegravir levels (186 during the initial oral administration phase and 852 after intramuscular injection). Cabotegravir pharmacokinetics was best described using a one-compartment model with distinct first order-absorption for oral and intramuscular administrations, and identical volume and clearance. Our model showed almost 40% faster absorption and 30% higher clearance than previously reported, resulting in a time to steady-state of 8 months and an elimination half-life of 4.6 weeks for long-acting cabotegravir. Sex and body mass index significantly influenced absorption, and bodyweight affected clearance. Model-based simulations showed that cabotegravir trough concentrations in females were 25% lower 4 weeks after the intramuscular loading dose, but 42% higher during the late maintenance phase. Finally, simulations indicated that in females, despite significantly higher cabotegravir concentrations, longer intervals between injections may not consistently ensure levels above the 4-fold protein-adjusted 90% inhibitory target concentration.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
I Abela
(I)
K Aebi-Popp
(K)
A Anagnostopoulos
(A)
M Battegay
(M)
E Bernasconi
(E)
D L Braun
(DL)
H C Bucher
(HC)
A Calmy
(A)
M Cavassini
(M)
A Ciuffi
(A)
G Dollenmaier
(G)
M Egger
(M)
L Elzi
(L)
J Fehr
(J)
J Fellay
(J)
H Furrer
(H)
C A Fux
(CA)
H F Günthard
(HF)
A Hachfeld
(A)
D Haerry
(D)
B Hasse
(B)
H H Hirsch
(HH)
M Hoffmann
(M)
I Hösli
(I)
M Huber
(M)
D Jackson-Perry
(D)
C R Kahlert
(CR)
L Kaiser
(L)
O Keiser
(O)
T Klimkait
(T)
R D Kouyos
(RD)
H Kovari
(H)
K Kusejko
(K)
N Labhardt
(N)
K Leuzinger
(K)
B Martinez de Tejada
(B)
C Marzolini
(C)
K J Metzner
(KJ)
N Müller
(N)
J Nemeth
(J)
D Nicca
(D)
J Notter
(J)
P Paioni
(P)
G Pantaleo
(G)
M Perreau
(M)
A Rauch
(A)
L Salazar-Vizcaya
(L)
P Schmid
(P)
R Speck
(R)
M Stöckle
(M)
P Tarr
(P)
A Trkola
(A)
G Wandeler
(G)
M Weisser
(M)
S Yerly
(S)
Informations de copyright
© 2024 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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