Table 2.
Overview of the current opioid pharmacokinetic studies in humans undergoing bariatric surgery. (↑ = increase; ↓ = decrease; ? = unknown).
| Morphine [58] | Morphine [59] | Oxycodone [60] | Oxycodone * [61] | Buprenorphine [62] | Methadone [63] | |
|---|---|---|---|---|---|---|
| Galenic oral formulation | Oral solution | Prolonged release | Oral solution vs. controlled release (lipid-based vs. water-swellable) | Prolonged release | Sublingual tablet | Oral capsule |
| Procedure | RYGB | RYGB | RYGB | Total gastrectomy | SG | SG |
| Study population | 30 patients (men/women) | 12 women | 21 patients (men/women) | 24 patients (men/women) | 1 women (case report) |
1 women (case report) |
| Controls | Before-after surgery | Matched controls | Reference PK/PD model in healthy volunteers | Healthy subjects (reference publications) | / | / |
| Blood sample timing | 3 visits: * V0: before * V1: +7–15 days * V2: +6 months |
12 samples 2 years after surgery | 12 samples at least 1 year after surgery | 12 samples in 5–12 days after surgery | 4 visits: * V0: before * V1: +1 week * V2: +1 month * V3: +1 year |
4 visits: * V0: 8 days before * V1: +5 days * V2: + 1 month * V3: +7 months |
| Tmax | * V0 vs. V1: ↓ (−2×) * V0 vs. V2: ↓ (−7.5×) |
= (control: 3.0 (1.5–5.0) h vs. patient: 2.6 (1.4–6.0) |
Controlled release: absorption lag time ↓ (control: 14 min vs. patient: 11.5 min) No PK differences between CR formulations |
↓ (control: 3 h vs. patient: 2.2 h) |
* V0 vs. V1: ↓ (0.8 h → 0.5 h) * V0 vs. V2: ↓ (0.8 h → 0.5 h) * V0 vs. V3: ↑ (0.8 h → 1 h) |
* V0 vs. V1: ↓ (2.5 h → 1.5 h) * V0 vs. V2: ↓ (2.5 h → 1.5 h) * V0 vs. V3: ↓ (2.5 h → 1 h) |
| Cmax | * V0 vs. V1: ↑ (1.7×) * V0 vs. V2: ↑ (3.3×) |
= (control: 16 (4–29) nM vs. patient: 11 (7–67) nM; p = 0.72) |
No data | = (control: 10.6 vs. patient: 12.97 ng/mL) |
* V0 vs. V1: ↑ (11.2 → 20.7 nmol/L) * V0 vs. V2: ↓ (11.2 → 8.1 nmol/L) * V0 vs. V3: ↓ (11.2 → 10.0 nmol/L) |
* V0 vs. V1: ↑ (945 → 1414 nmol/L) * V0 vs. V2: ↑ (945 → 2128 nmol/L) * V0 vs. V3: ↑ (945 → 2564 nmol/L) |
| AUC | V0 vs. V1: ↑ (+23.4%) V0 vs. V2: ↑ (+55.5%) |
= (control: 80 (34–156) nmol.hr/L vs. patient: 66 (32–406) nmol.hr; p = 0.71) |
↑ (+14.4%) | ? | * V0 vs. V1: ↓ (−6.3%) * V0 vs. V2: ↓ (−43%) * V0 vs. V3: ↓ (−42%) |
* V0 vs. V1: ↑ (+41%) * V0 vs. V2: ↑ (+143%) * V0 vs. V3: ↑ (+213%) |
| Advice | Divide dose | No dose reduction | Bioequivalence demonstrated for both CR formulations | No dose reduction | Perioperative monitoring | Perioperative monitoring |
Abbreviations: CR = controlled release; PD = pharmacodynamic; PK = pharmacokinetic; SG = sleeve gastrectomy; RYGB = Roux-en-Y Gastric Bypass; V = visit. * Total gastrectomy with Roux-en-Y reconstruction was performed in an oncologic setting and not for weight loss.