Dirlotapide
Dirlotapide is a selective **gut microsomal triglyceride transfer protein (GMTP) inhibitor** indicated specifically for the management of obesity in dogs. By acting locally in the gastrointestinal tract, it reduces dietary fat absorption and promotes a feeling of satiety, effectively decreasing appetite and begging behaviors. > **Clinical Pearl:** Dirlotapide requires a highly structured, mathematically driven dosing protocol based on weekly weight loss targets. It is strictly contraindicated in cats due to the high risk of inducing hepatic lipidosis during rapid weight loss. While the drug is absorbed systemically, its primary efficacy is driven by local action in the gut. Systemic absorption is more closely correlated with adverse effects rather than weight loss efficacy. Successful long-term weight management requires concurrent dietary and lifestyle modifications.
Mecanismo: Dirlotapide selectively inhibits **microsomal triglyceride transfer protein (GMTP)** in the enterocytes of the gut. * **Lipid Blockade:** Inhibits GMTP → blocks the assembly and release of lipoproteins into systemic circulation → reduces dietary fat absorption. * **Satiety Signaling:** The accumulation of lipids within enterocytes triggers the release of **Peptide YY (PYY)** into the systemic circulation → signals the central nervous system to decrease appetite and induce satiety. * **Action Site:** Primarily acts locally in the gut. Systemic blood levels do not directly correlate with efficacy, but rather with systemic toxicity.
Dosificación por especie
- Weight Loss Phase (First 14 days) · 0.01 mL/kg (0.05 mg/kg) · PO · q24h · 14 days · Initial assessment required prior to therapy.
- Weight Loss Phase (Days 15 to 28) · 0.02 mL/kg (0.1 mg/kg) · PO · q24h · 14 days · Double the initial dose volume.
- Weight Loss Phase (Subsequent Months) · Adjust volume monthly to maintain a target percent weight loss of ≥ 0.7% per week. Max dose: 0.2 mL/kg (0.09 mL/lb) · PO · q24h · Until desired weight is reached · If target not met: increase dose by 100% (first adjustment) or 50% (subsequent adjustments). If food consumption is greatly reduced, withhold 1-2 days.
- Weight Management Phase · Adjust dose volume by -50%, 0%, or +50% based on last month's weight loss, then +/- 25% in subsequent months. Max dose: 0.2 mL/kg (0.09 mL/lb) · PO · q24h · 3 months recommended · Establish optimal food intake and physical activity to stabilize body weight.
Las dosis son una referencia clínica para médicos veterinarios. Confirme siempre con la información vigente del producto y el paciente individual.
Vías de administración
Contraindicaciones
- Cats (high risk of hepatic lipidosis)
- Dogs with liver disease
- Dogs receiving long-term corticosteroid therapy
- Unmanaged endocrine disease (e.g., hyperadrenocorticism/Cushing's disease)
Efectos adversos
- Vomiting (especially during the first month or 3-4 hours post-dose)
- Diarrhea
- Lethargy
- Anorexia
- Salivation
- Constipation
- Dehydration
- Elevated serum hepatic transaminases
Interacciones farmacológicas
- Narrow therapeutic index oral drugs · Potential altered absorption rate and extent; administer at least 2 hours prior to dirlotapide.
- Fat-soluble vitamins (A, E, K) · Decreased plasma concentrations during the initial treatment phase; levels typically stabilize and recover during the weight stabilization phase.
Monitoreo
- Patient weight (monthly, to guide dose adjustments)
- Adverse gastrointestinal effects (vomiting, diarrhea, anorexia)
- Liver enzymes (baseline and occasional monitoring)
Sobredosis
**Toxicity Profile:** Oral doses of 0.5, 1, and 2 mL/kg (2.5X, 5X, and 10X the maximum labeled dose) administered to normal weight Beagles for two weeks were generally tolerated. **Clinical Signs of Overdose:** * Vomiting and diarrhea * Anorexia and lethargy * Transient elevations in liver enzymes (transaminases) *Note: No histopathologic evidence of hepatic necrosis was observed at these doses.*
La referencia de fármacos de VetSheet está destinada a médicos veterinarios como apoyo a la decisión clínica; no sustituye el juicio profesional ni la información vigente del fabricante.