Table 4:
AUC0-t/∞ [mg ·h/L]a Simulated/ observed (ratio) |
Cmax [mg/L] Simulated/ observed (ratio) |
tmax [h] Simulated/ observed (ratio) |
|
---|---|---|---|
Dolutegravir | |||
Non-pregnant women | |||
Castellino study [17] | 34.0/35.9 (0.95) | 2.29/2.53 (0.86) | 0.95/0.50 (1.90) |
Dooley study cohort 1 [18] (steady state) | 39.0/36.1 (1.08) | 2.91/2.65 (1.10) | 2.25/1.5 (1.50) |
Dooley study cohort 2 [18] (steady state) | 41.1/42.1 (0.98) | 2.96/2.91 (1.02) | 2.20/2.00 (1.10) |
Ford study [23] (steady state) | 63.1/52.5(1. 20) | 4.00/3.43 (1.17) | 4.25/4.00 (1.06) |
Johnson2014, Cohort 1 (steady state) [24] | 65.2/71.9 (0.91) | 4.14/4.35 (0.95) | 4.30/3.00 (1.43) |
Johnson2014, Cohort2 (steady state) [24] | 67.4/71.9 (0.94) | 4.30/4.78 (0.90) | 4.30/3.50 (1.23) |
Song2012_high_fat [21] | 66.1/83.6 (0.79) | 2.97/4.19 (0.71) | 4.90/5.00 (0.98) |
Song2012_low_fat [21] | 59.8/66.7 (0.90) | 2.83/3.81 (0.74) | 4.00/3.00 (1.33) |
Song2012_moderate_fat [21] | 64.7/71.0 (0.91) | 2.94/3.86 (0.76) | 4.75/4.00 (1.19) |
Song2016_moderate_fat_meal [20] (steady state) | 62.2/55.4 (1.12) | 3.99/3.83 (1.04) | 4.00/3.00 (1.33) |
Song2013 study [19] b | 47.2/40.3 (1.17) | 1.82/1.90 (0.96) | 2.50/3.00 (0.83) |
Weller study [22] | 44.1/37.1 (1.19) | 1.89/1.84 (1.03) | 2.40/2.50 (0.96) |
Wang2019 [25] | 63.8/51.62 (1.23) | 4.30/3.81(1.13) | 4.10/4.00 (1.03) |
Pregnant women | |||
2nd trimester (steady state) | 34.70/42.38 (0.82) | 2.77/3.00 (0.92) | 4.20/2.00 (2.10) |
3rd trimester (steady state) | 31.91/47.59 (0.67) | 2.57/3.00 (0.86) | 4.20/4.00 (1.05) |
Raltegravir | |||
Non-pregnant women | See OSP GitHub | See OSP GitHub | See OSP GitHub |
Markowitz2006[75] | 8.86/7.96 (1.11) | 3.04/2.24 (1.36) | 0.80/1.00 (0.80) |
Iwamoto2009[78] | 8.66/4.90 (1.77) | 3.10/1.28 (2.42) | 0.75/1.50 (0.50) |
Rhee2014 [76] | 9.13/8.53 (1.07) | 3.11/2.22 (1.40) | 0.75/2.00 (0.38) |
Wenning2009 [77] | 8.99/12.25 (0.73) | 3.12/3.82 (0.81) | 0.75/1.50 (0.50) |
Brainard2011_fasted b [79] | 9.66/6.47 (1.49) | 3.42/1.59 (2.15) | 0.75/2.00 (0.38) |
Brainard2011_high fat b [79] | 8.83/ 11.37 (0.78) | 1.48/1.59 (0.93) | 2.45/2.00 (1.23) |
Brainard2011_moderate_fat b [79] | 8.86/6.44 (1.38) | 1.54/0.74 (2.08) | 2.20/4.00 (0.55) |
Brainard2011_low_fat b [79] | 9.01/3.39 (2.66) | 1.76/0.59 (2.98) | 1.95/3.50 (0.56) |
Taburet2015_moderate_fat_1 c[80] | 8.46/8.24 (1.03) | 1.65/2.03 (0.82) | 2.20/1.00 (2.20) |
Taburet2015_moderate_fat_2 c [80] | 8.95/ 11.00 (0.81) | 1.54/2.77 (0.56) | 2.20/2.00 (1.10) |
Pregnant women | |||
2nd trimester (steady state) | 4.10/3.90 (1.05) | 0.834/0.67 (1.22) | 2.55/2.00 (1.28) |
3rd trimester (steady state) | 3.71/4.44 (0.84) | 0.763/0.85 (0.89) | 2.50/2.00 (1.25) |
Data expressed as geometric mean values unless indicated otherwise.
AUC0-t was used in the studies by Dooley et al. [18], Ford et al. [23], Johnson et al. [24], Song et al. [20], Markowitz et al.,[75] Brainard et al.[79] and Taburet et al.[80]; whereas AUC0-∞ was used in the studies by Castellino et al. [17], Song et al. [21], Song et al. [19], Weller et al. [22], Iwamoto et al.[78], Rhee et al.[76] and Wenning et al.[77].
Data expressed as arithmetic mean values.
Data expressed as median values.
Abbreviations: AUC0-t: area under the concentration-time curve from zero to the time point of the last observed plasma concentration (in case of multiple dose studies, time refers to the time after last dose); AUC0-∞: area under the concentration-time curve from zero to infinity; Cmax: peak plasma concentration; tmax: time at which peak plasma concentration is reached.