Table 2.
Summary of dolutegravir pharmacokinetic parameters by weight band and published adult reference values
| 3 kg to <6 kg (<6 months) | 6 kg to <10 kg | 10 kg to <14 kg | 14 kg to <20 kg | 14 kg to <20 kg | Adult (≥40 kg)12 | Adult (≥40 kg)13, 14 | |
|---|---|---|---|---|---|---|---|
| Dose | 5 mg | 15 mg | 20 mg | 25 mg | 25 mg | 50 mg (once daily) | 50 mg (twice daily) |
| Formulation | DT | DT | DT | DT | FCT | FCT | FCT |
| Number of participants with pharmacokinetic profiles | 5 | 13 | 11 | 16* | 19* | 10† | 24‡ |
| Age on pharmacokinetic assessment day (years) | 0·3 (0·3–0·4) | 1·4 (1·1–2·0) | 2·7 (2·0–3·3) | 6·0 (5·2–6·9) | 6·2 (5·1–7·4) | .. | .. |
| Weight on pharmacokinetic assessment day (kg) | 5·3 (4·9–5·3) | 8·4 (7·1–9·6) | 10·9 (10·3–12·0) | 17·9 (15·5–18·6) | 17·0 (16·0–18·6) | .. | .. |
| Dose (mg/kg) | 0·9 (0·9–1·0) | 1·8 (1·6–2·1) | 1·8 (1·7–1·9) | 1·4 (1·3–1·6) | 1·5 (1·3–1·6) | .. | .. |
| Previous dolutegravir exposure on pharmacokinetic assessment day (weeks) | 2·1 (2·1–4·0) | 4·0 (3·0–5·9) | 2·1 (2·0–17·9) | 30·9 (25·9–41·3) | 2·0 (1·9–3·4) | .. | .. |
| C0 (mg/L) | 0·52 (75%) | 0·46 (302%) | 0·79 (59%) | 0·98 (52%) | 0·60 (74%) | .. | 3·20 (69%) |
| Ctrough (mg/L) | 0·64 (51%) | 0·53 (150%) | 0·77 (57%) | 0·87 (64%) | 0·44 (50%) | 0·83 (26%) | 2·72 (70%) |
| Number of participants below EC90 | 0 | 4/13 (31%) | 0 | 0 | 4/19 (21%) | .. | .. |
| AUC0–24 h (h × mg/L) | 45·20 (33%) | 52·23 (72%) | 76·10 (21%) | 69·93 (28%) | 39·57 (32%) | 43·4 (20%) | 93·4 (50%)§ |
| Cmax (mg/L) | 4·00 (32%) | 5·61 (47%) | 8·06 (21%) | 7·20 (19%) | 4·03 (31%) | 3·34 (16%) | 5·41 (40%) |
| Tmax (h) | 2·0 (1·0–2·0) | 2·0 (1·0–2·2) | 2·0 (2·0–2·3) | 2·0 (2·0–2·0) | 2·0 (2·0–2·0) | 2·0 (1·0–4·0) | 2·0 (0–7·9) |
| T1/2 (h) | 8·79 (22%) | 6·98 (29%) | 6·95 (27%) | 8·00 (32%) | 7·28 (21%) | 12·0 (22%) | .. |
| Oral clearance (L/h) | 0·11 (33%) | 0·29 (72%) | 0·26 (21%) | 0·36 (28%) | 0·63 (32%) | 1·15 (20%)¶ | 0·54 (70%)¶ |
| Volume of distribution (L) | 1·40 (34%) | 2·89 (43%) | 2·63 (25%) | 4·13 (19%) | 6·64 (34%) | .. | .. |
Data are n, geometric mean (coefficient of variation percentage), median (IQR), or n/N (%), unless otherwise specified. None were below IC90 0·064 mg/L. Only one child who was 6 months or older in the 3 kg to less than 6 kg weight band receiving 10 mg dispersible tablet had an eligible pharmacokinetic curve (appendix p 3). AUC0–24h=area under the concentration-time curve from 0 to 24 h. DT=dispersible tablet. FCT=film-coated tablet. C0=baseline concentration. Cmax=maximum plasma concentration. Ctrough=trough concentration. EC90=the effective concentration at which 90% of maximal viral inhibition is achieved in a 10-day monotherapy study. IC90=90% inhibitory concentration. T1/2=apparent elimination half-life. Tmax=time to maximum plasma concentration.
Nine participants had pharmacokinetic profiles on both film-coated tablets and dispersible tablets.
Fasted adults who were HIV positive.
Adults who were HIV positive and had previous treatment, fed state was not specified.
Calculated by doubling AUC0–12 h.
Calculated by dividing dose over AUC0–24 h.