PMID- 11399983
OWN - NLM
STAT- MEDLINE
DCOM- 20010913
LR  - 20201208
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 15
IP  - 8
DP  - 2001 May 25
TI  - Pharmacokinetics and safety of amprenavir and ritonavir following multiple-dose, 
      co-administration to healthy volunteers.
PG  - 1009-18
AB  - OBJECTIVE: To evaluate the safety and pharmacokinetic interaction between 
      amprenavir (APV) and ritonavir (RTV). METHODS: Three open-label, randomized, 
      two-sequence, multiple-dose studies having the same design (7 days of APV or RTV 
      alone followed by 7 days of both drugs together) used 450 or 900 mg APV with 100 
      or 300 mg RTV every 12 h with pharmacokinetic assessments on days 7 and 14. 
      Safety was monitored as clinical adverse events (AEs) and laboratory 
      abnormalities. RESULTS: Relative to APV alone, RTV co-administration resulted in 
      a 3.3- to 4-fold and 10.84 to 14.25-fold increase in the geometric least-square 
      (GLS) mean area under the plasma concentration--time curve (AUC(tau,ss)) and 
      minimum concentration (C(min,ss)), respectively. APV 900 mg with RTV 100 mg 
      resulted in a 2.09-fold and 6.85-fold increase in the GLS mean AUC(tau,ss) and 
      C(min,ss), respectively. On day 14, the geometric mean (95% confidence interval) 
      for 450 mg APV AUC(tau,ss) (micro x h/mL) was 23.49 (19.32--28.57) with 300 mg 
      RTV and 35.42 (30.46--44.42) with 100 microg RTV, and for the 900 mg APV with 100 
      mg RTV 47.11 (39.47--61.24). The 450 mg APV C(min,ss) (microg/ml) were 1.32 
      (1.05--1.67) and 2.01 (1.70--2.61), and 2.47 (2.08--3.32) for 900 mg APV. The 
      most common AEs were mild and included diarrhea, nausea/vomiting, oral 
      parasthesias, and rash. The triglyceride and cholesterol increased significantly 
      from RTV exposure. CONCLUSION: Adding RTV to APV resulted in clinically and 
      statistically significant increases in APV AUC and C(min) with variable effects 
      on maximum concentration. The two RTV doses had similar effects on APV but AEs 
      were more frequent with 300 mg RTV.
FAU - Sadler, B M
AU  - Sadler BM
AD  - Division of Clinical Pharmacology, GlaxoSmithKline, Research Triangle Park, North 
      Carolina 27709, USA.
FAU - Piliero, P J
AU  - Piliero PJ
FAU - Preston, S L
AU  - Preston SL
FAU - Lloyd, P P
AU  - Lloyd PP
FAU - Lou, Y
AU  - Lou Y
FAU - Stein, D S
AU  - Stein DS
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Carbamates)
RN  - 0 (Furans)
RN  - 0 (HIV Protease Inhibitors)
RN  - 0 (Sulfonamides)
RN  - 5S0W860XNR (amprenavir)
RN  - O3J8G9O825 (Ritonavir)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Body Mass Index
MH  - Carbamates
MH  - Diarrhea/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Exanthema/chemically induced
MH  - Female
MH  - Furans
MH  - HIV Protease Inhibitors/administration & dosage/adverse effects/*pharmacokinetics
MH  - HIV Seronegativity
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nausea/chemically induced
MH  - Ritonavir/administration & dosage/adverse effects/*pharmacokinetics
MH  - Statistics, Nonparametric
MH  - Sulfonamides/administration & dosage/adverse effects/*pharmacokinetics
EDAT- 2001/06/16 10:00
MHDA- 2001/09/14 10:01
CRDT- 2001/06/16 10:00
PHST- 2001/06/16 10:00 [pubmed]
PHST- 2001/09/14 10:01 [medline]
PHST- 2001/06/16 10:00 [entrez]
AID - 10.1097/00002030-200105250-00009 [doi]
PST - ppublish
SO  - AIDS. 2001 May 25;15(8):1009-18. doi: 10.1097/00002030-200105250-00009.