Assessment of the Effects of Steady-State Bupropion on the Pharmacokinetic Profile of Zolpidem in Healthy Volunteers

Abstract

The study's purpose was to evaluate if bupropion, an antidepressant agent, can influence the pharmacokinetic profile of zolpidem, a sedative/hypnotic drug, and its main metabolite (zolpidem phenyl-4-carboxylic acid, Z4CA). The open-label, non-randomized, sequential clinical trial consisted of two periods: Period 1, when each volunteer received a single dose of zolpidem 5 mg and Period 2, when a combination of zolpidem 5 mg and bupropion 300 mg was administered, after a 7-day pre-treatment with bupropion. Pharmacokinetic analysis used for the non-compartmental approach and safety evaluations were conducted during the study. Bupropion pre-treatment decreased mean C max and AUC 0-∞ for zolpidem and increased the same parameters for Z4CA. Most of zolpidem's pharmacokinetic parameters displayed statistically significant differences between study periods. These results demonstrated that a pharmacokinetic interaction does occur between these drugs, possibly due to CYP3A4 induction, hypothesis which needs to be further investigated. RezumatScopul studiului a fost de a evalua dacă bupropiona, un antidepresiv, poate influența profilul farmacocinetic al zolpidemului, un sedativ/hipnotic, și al principalului său metabolit (zolpidem acid fenil-4-carboxilic, Z4CA). Studiul clinic deschis, nonrandomizat, secvențial a constat în două perioade: Perioada 1, când fiecare voluntar a primit o doză unică de zolpidem 5 mg și Perioada 2, când s-au co-administrat zolpidem 5 mg și bupropionă 300 mg, după 7 zile de pre-tratament cu bupropionă. Analiza farmacocinetică a utilizat metoda non-compartimentală, iar în timpul studiului s-a urmărit și evaluarea siguranței terapiei. Pre-tratamentul cu bupropionă a scăzut valoarea medie a C max și AUC 0-∞ pentru zolpidem și a crescut aceiași parametri pentru Z4CA. Majoritatea parametrilor farmacocinetici ai zolpidemului au prezentat diferențe semnificative statistic între perioadele de studiu. Aceste rezultate au demonstrat că există o interacțiune farmacocinetică între aceste medicamente, posibil datorită inducției CYP3A4, ipoteză care trebuie investigată în continuare.

Evaluation of Physiologically Based Pharmacokinetic Models to Predict the Absorption of BCS Class I Drugs in Different Pediatric Age Groups

“…The scale and shape parameters were fitted to reported dissolution profiles of zolpidem IR tablets measured in fasted‐state simulated intestinal fluid in vitro 30 . Thereafter, the fitted parameter values were transferred to PK‐Sim, and the specific intestinal permeability was fitted to pharmacokinetic data in the fasted state from multiple clinical studies 27,28,31–33 . Another independent set of clinical data not used during parameter optimization was thereafter used to evaluate the adult PBPK model 34–45 …”

New Approaches of the Hyponatremia Treatment in the Elderly – An Update

“…Frequently, the inappropriate secretion of the antidiuretic hormone syndrome (SIADH) is incriminated (Figure 1) [12,13]. The nonhypotonic hyponatremia (isotonic or hypertonic) [4], as a dilutional hNa [14], is generated by the accumulation of effective osmoles in the plasma concentration, replacing the water from the intracellular to the extracellular extent [14,15]. According to the concentration of the plasma compounds, normal or enhanced values of the osmolality may be depicted (Figure 1).…”

Influence of Fluvoxamine on Carvedilol’s Pharmacokinetics in Rats

“…Fluvoxamine is an antidepressant agent which belongs to the selective serotonin reuptake inhibitors, SSRIs [11,14] and is used in patients with depression or other psychiatric diseases [13,20]. It has a good absorption (more than 90%) and a low plasma protein binding (77%), being metabolized in the liver and excreted in urine [9,10,16].…”