Development of Aqueous Parenteral Formulations for Carbamazepine through the Use of Modified Cyclodextrins

Brewster, Marcus E.; Anderson, Wesley R.; Estes, Kerry S.; Bodor, Nicholas

doi:10.1002/jps.2600800420

Cited by 67 publications

(58 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the 78 last decade, a new Cremophor EL-free formulation of alfaxalone (3±-hydroxy-5±-79 pregnane-11,20-dione), without alfadolone, has been developed for use in small animals 80 and registered in Australia, New Zealand, South Africa and the UK (Alfaxan, Vétoquinol, 81 UK). The new formulation uses a cyclodextrin base (2-hydroxypropyl-β-cyclodextrin, 82 HPCD) as solubilizing agent and does not cause histamine release [15,16]. Alfaxalone 83 was shown to provide a rapid and smooth induction of anesthesia with rapid recovery of 84 consciousness and minimal respiratory depression at clinical doses [16,17].…”

Section: Objective: To Compare Alfaxalone and Propofol As Anesthetic mentioning

confidence: 99%

Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol

Doebeli

Michel

Bettschart‐Wolfensberger

et al. 2013

Theriogenology

View full text Add to dashboard Cite

The effects of alfaxalone and propofol on neonatal vitality were studied in 22 bitches and 81 puppies after their use as anesthetic induction agents for emergency cesarean section. After assessment that surgery was indicated, bitches were randomly allocated to receive alfaxalone 1 to 2 mg/kg body weight or propofol 2 to 6 mg/kg body weight for anesthetic induction. Both drugs were administered intravenously to effect to allow endotracheal intubation, and anesthesia was maintained with isoflurane in oxygen. Neonatal vitality was assessed using a modified Apgar score that took into account heart rate, respiratory effort, reflex irritability, motility, and mucous membrane color (maximum score = 10); scores were assigned at 5, 15, and 60 minutes after delivery. Neither the number of puppies delivered nor the proportion of surviving puppies up to 3 months after delivery differed between groups. Anesthetic induction drug and time of scoring were associated with the Apgar score, but delivery time was not. Apgar scores in the alfaxalone group were greater than those in the propofol group at 5, 15, and 60 minutes after delivery; the overall estimated score difference between the groups was 3.3 (confidence interval 95%: 1.6-4.9; P < 0.001). In conclusion, both alfaxalone and propofol can be safely used for induction of anesthesia in bitches undergoing emergency cesarean section. Although puppy survival was similar after the use of these drugs, alfaxalone was associated with better neonatal vitality during the first 60 minutes after delivery. respectively). The estimated group effect was a difference of 3.3, CI 95 % (1.6;4.9) (P < 40 0.001). Neither the number of delivered puppies nor the proportion of surviving puppies 60 41 min post-delivery differed between the groups (P = 0.168 and P = 0.149, respectively). 42Conclusions: Induction of anesthesia with alfaxalone was associated with higher 43 neonatal Apgar score. Both protocols can be safely used for induction of anesthesia in 44 dogs undergoing emergency cesarean section. 45

show abstract

Section: Objective: To Compare Alfaxalone and Propofol As Anesthetic mentioning

confidence: 99%

Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol

Doebeli

Michel

Bettschart‐Wolfensberger

et al. 2013

Theriogenology

View full text Add to dashboard Cite

show abstract

“…Activation by 10 mM 3a-hydroxy5a-pregnan-20-one (3a5aP) or 3a-hydroxy-5b-pregnan-20-one (3a5bP) also resulted in prominent responses (42 6 18%, 8 cells, and 45 6 19%, 4 cells, respectively). Ten micromolar is a saturating concentration for these steroids in terms of potentiation and activation (Shu et al, 2004), and is near the limit of solubility in aqueous solutions (Brewster et al, 1989). Testosterone, 17b-estradiol, dehydroepiandrosterone (DHEA), pregnenolone sulfate, and DHEA sulfate did not elicit current responses, although in some cases (e.g., in the presence of 10 mM DHEA sulfate) rebound currents following termination of steroid application were observed.…”

mentioning

confidence: 99%

γ-Aminobutyric Acid Type A α4, β2, and δ Subunits Assemble to Produce More Than One Functionally Distinct Receptor Type

et al. 2014

View full text Add to dashboard Cite

Native g-aminobutyric acid (GABA) A receptors consisting of a4, b1-3, and d subunits mediate responses to the low, tonic concentration of GABA present in the extracellular milieu. Previous studies on heterologously expressed a4bd receptors have shown a large degree of variability in functional properties, including sensitivity to the transmitter. We studied properties of a4b2d receptors employing free subunits and concatemeric constructs, expressed in Xenopus oocytes, HEK 293 cells, and cultured hippocampal neurons. The expression system had a strong effect on the properties of receptors containing free subunits. The midpoint of GABA activation curve was 10 nM for receptors in oocytes versus 2300 nM in HEK cells. Receptors activated by the steroid alfaxalone had an estimated maximal open probability of 0.6 in oocytes and 0.01 in HEK cells. Irrespective of the expression system, receptors resulting from combining the tandem construct b2-d and a free a4 subunit exhibited large steroid responses. We propose that free a4, b2, and d subunits assemble in different configurations with distinct properties in oocytes and HEK cells, and that subunit linkage can overcome the expression system-dependent preferential assembly of free subunits. Hippocampal neurons transfected with a4 and the picrotoxin-resistant d(T269Y) subunit showed large responses to alfaxalone in the presence of picrotoxin, suggesting that a4bd receptors may assemble in a similar configuration in neurons and oocytes.

show abstract

“…Nevertheless, introducing hydroxypropy l groups on b -CD molecules has enabled the administration of higher doses of CDs in vivo. For instance, intravenous doses of 40 g/kg in rabbits (Irie et al 1992), 10 g/kg in monkeys (Brewster et al 1991), and 30 g (total) in humans (Carpenter et al 1995) have been administered with no adverse effects. Nevertheless, caution has to be taken since hpb -CD has been documented to induce pulmonary edema in dogs and cause occasional distress or agitation in rabbits (Carpenter et al 1995).…”

Section: Cyclodextrins and Toxicitymentioning

confidence: 99%

“…CDs have been utilized for delivery of pharmacologically active hydrophobi c compounds within polar environments. Some of the therapeutic agents so complexed include estradiol (Brewster et al 1988), testosterone (Muller and Albers 1991; Salehian et al 1995), b -sitosterol, the main dietary phytosterol (Awad et al 1996), and the antiepileptic drug carbamazepine (Brewster et al 1991(Brewster et al , 1988(Brewster et al , 1997. Apart from drug molecules, CDs are used to host sterols such as 27-OHcholesterol and cholesterol (Winegar et al 1996).…”

Section: Introduction To Cyclodextrinsmentioning

confidence: 99%

Apolipoprotein A-I, Phospholipid Vesicles, and Cyclodextrins as Potential Anti-Atherosclerotic Drugs: Delivery, Pharmacokinetics, and Efficacy

Dass

2000

Drug Delivery

View full text Add to dashboard Cite

show abstract

Development of Aqueous Parenteral Formulations for Carbamazepine through the Use of Modified Cyclodextrins

Cited by 67 publications

References 8 publications

Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol

Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol

γ-Aminobutyric Acid Type A α4, β2, and δ Subunits Assemble to Produce More Than One Functionally Distinct Receptor Type

Apolipoprotein A-I, Phospholipid Vesicles, and Cyclodextrins as Potential Anti-Atherosclerotic Drugs: Delivery, Pharmacokinetics, and Efficacy

Contact Info

Product

Resources

About