Physicochemical interaction of local anesthetics with lipid model systems—correlation with in vitro permeation and in vivo efficacy

Welin-Berger, Katayoun; Neelissen, Jan; Engblom, Johan

doi:10.1016/s0168-3659(02)00035-4

Cited by 12 publications

(7 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This phenomenon was accordance with another in vitro study, which reported that the skin permeability of lidocaine was higher than prilocaine. 20) In Table 1, the values of T 1/2b were significantly different between EMLA and the P-L formulation, which might be explained as different reserve effects of skin for the two formulations since EMLA had higher affinity to skin than the hydrophilic P-L formulation. The residual drug released form the P-L formulation, even after its removal, were higher than that from EMLA, resulting in different drug elimination rates in the dermis.…”

Section: Fig 3 Relative Recovery Of Lidocaine and Prilocaine Of Sixmentioning

confidence: 93%

Percutaneous Penetration Kinetics of Lidocaine and Prilocaine in Two Local Anesthetic Formulations Assessed by in Vivo Microdialysis in Pigs

Hui-lin

Chen

et al. 2007

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The aim of this study was to characterize and compare the percutaneous penetration kinetics of lidocaine (L) and prilocaine (P) in two local anesthetic formulations by in vivo microdialysis coupled with HPLC. The microdialysis system for studying lidocaine and prilocaine was calibrated by a no-net-flux method in vitro and retrodialysis method in vivo, respectively. A dosage of 0.2 g/cm2 of an in-house P-L formulation (2.5% lidocaine and 2.5% prilocaine, methylcellulose-based) and commercially available Eutectic Mixture of Local Anesthesia (EMLA, 2.5% lidocaine and 2.5% prilocaine, carbopol-based) was separately but symmetrically applied in the dorsal region of pigs. Saline (0.9%, w/v) was perfused into the linear microdialysis probe at a flow rate of 1.5 microl/min. Dialysate was collected upon topical application up to 6 h at 20-min intervals and assessed by HPLC. The results demonstrated the area under the concentration-time curve (AUC(0-6 h)) of lidocaine and prilocaine in EMLA was 71.95+/-23.36 microg h/ml and 38.01+/-14.8 microg h/ml, respectively, in comparison to 167.11+/-56.12 microg h/ml and 87.02+/-30.38 microg h/ml in the P-L formulation. The maximal concentrations (Cmax) of lidocaine and prilocaine in the dermis were 29.2+/-9.08 microg/ml and 16.54+/-5.31 microg/ml in EMLA and 80.93+/-17.98 microg/ml and 43.69+/-12.87 microg/ml in the P-L formulation, respectively. This study indicates a well-calibrated microdialysis system can provide vital real-time information on percutaneous drug delivery and specifically a methylcellulose-based P-L formulation can increase percutaneous absorption of both lidocaine and prilocaine in pigs compared to carbopol-based EMLA.

show abstract

Section: Fig 3 Relative Recovery Of Lidocaine and Prilocaine Of Sixmentioning

confidence: 93%

Percutaneous Penetration Kinetics of Lidocaine and Prilocaine in Two Local Anesthetic Formulations Assessed by in Vivo Microdialysis in Pigs

Hui-lin

Chen

et al. 2007

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…The structural transitions depend on interactions between the lipid and the guest molecule, and the quantity entrapped. − Certain compounds reduce the bilayer curvature. This was demonstrated recently with sodium diclofenac (Na-DFC), where increasing quantities of the solubilized drug in the discontinuous cubic Q L mesophase induced transitions to a bicontinuous cubic phase and eventually to a lamellar phase. , The rate of release of the encapsulated bioactives depends on the mesophase and bioactive structures, and on physicochemical interactions between these components. ,− It can be modulated if sufficient knowledge is gained on the structure of the mesophase. ,, …”

Section: Introductionmentioning

confidence: 99%

Solubilization of Hydrophobic Guest Molecules in the Monoolein Discontinuous Q_L Cubic Mesophase and Its Soft Nanoparticles

et al. 2008

View full text Add to dashboard Cite

Hydrophobic bioactive guest molecules were solubilized in the discontinuous cubic mesophase (QL) of monoolein. Their effects on the mesophase structure and thermal behavior, and on the formation of soft nanoparticles upon dispersion of the bulk mesophase were studied. Four additives were analyzed. They were classified into two types based on their presumed location within the lipid bilayer and their influence on the phase behavior and structure. Differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), polarized light microscopy, cryogenic-transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS) were used for the analysis. We found that carbamazepine and cholesterol (type I molecules) likely localize in the hydrophobic domains, but close to the hydrophobic-hydrophilic region. They induce strong perturbation to the mesophase packing by influencing both the order of the lipid acyl chains and interactions between lipid headgroups. This results in significant reduction of the phase transition enthalpy, and phase separation into lamellar and cubic mesophases above the maximum loading capacity. The inclusion of type I molecules in the mesophase also prevents the formation of soft nanoparticles with long-range internal order upon dispersion. In their presence, only vesicles or sponge-like nanoparticles form. Phytosterols and coenzyme Q10 (type II molecules) present only moderate effects. These molecules reside in the hydrophobic domains, where they cannot alter the lipid curvature or transform the QL mesophase into another phase. Therefore, above maximum loading, excess solubilizate precipitates in crystal forms. Moreover, when type II-loaded QL is dispersed, nanoparticles with long-range order and cubic symmetry (i.e., cubosomes) do form. A model for the growth of the ordered nanoparticles was developed from a series of intermediate structures identified by cryo-TEM. It proposes the development of the internal structure by fusion events between bilayer segments.

show abstract

“…This is explained by the larger volume of distribution of prilocaine and the higher clearance compared to lidocaine . Besides the lipophilic nature of the two medium‐duration local anesthetics is almost the same while their water solubility slightly differs . In a study by Wahl et al, it was concluded that there is no difference in pain response between injection of prilocaine plain and that of lidocaine with 1:100,000 epinephrine .…”

Section: Discussionmentioning

confidence: 99%

“…33,34 Besides the lipophilic nature of the two medium-duration local anesthetics is almost the same while their water solubility slightly differs. 35 In a study by Wahl et al, it was concluded that there is no difference in pain response between injection of prilocaine plain and that of lidocaine with 1:100,000 epinephrine. 36 The maximum recommended dose for lidocaine in the European countries is 200 mg without epinephrine and 500 mg of lidocaine is allowed if epinephrine (5 μg/mL) is added.…”

Section: Pericatheter Bleedingmentioning

confidence: 98%

Regional anesthesia with epinephrine‐containing lidocaine reduces pericatheter bleeding after tunneled hemodialysis catheter placement

Mutlu¹,

Koçak²,

Ulusan³

et al. 2018

Hemodialysis International

View full text Add to dashboard Cite

Introduction: Pericatheter bleeding (PB) following tunneled hemodialysis catheter (THC) placement is a common phenomenon. In addition to complicating securement of the THC, the PB may loosen the adhesive catheter dressing and delay wound healing. The primary aim of this study was to determine whether epinephrine‐containing local anesthetics rather than plain ones reduce superficial PB after THC placement. Methods: The study was based on the retrospective analysis of the prospectively gathered data. Forty‐six patients receiving local analgesia during THC placement were randomly assigned in a double‐blind manner to two groups according to local anesthetic mixtures used (n =22 to prilocaine group [group 1]; n =24 to epinephrine‐containing lidocaine group [group 2]). Presence or absence of PB after the THC placement was evaluated. Differences between groups with and without controlling other variables were statistically analyzed. Findings: Epinephrine‐containing lidocaine (group 2) significantly reduced PB in comparison with prilocaine, P = 0.003. Use of epinephrine‐containing lidocaine (group 2) was associated with a reduction in the likelihood of PB (Odds ratio = 0.017). Meanwhile, use of prilocaine (group 1) had 59.7 times higher odds in the likelihood of PB after THC placement. Lower rate of systolic blood pressure (SBP) in group 2 patients after 5 minutes of injections was also noted, P = 0.008. Epinephrine‐containing lidocaine was well tolerated and caused no significant cardiovascular disturbance. Discussion: Local infiltration of epinephrine‐containing lidocaine instead of plain local anesthetics during THC insertion may reduce superficial PB and improve patient comfort.

show abstract

Physicochemical interaction of local anesthetics with lipid model systems—correlation with in vitro permeation and in vivo efficacy

Cited by 12 publications

References 23 publications

Percutaneous Penetration Kinetics of Lidocaine and Prilocaine in Two Local Anesthetic Formulations Assessed by in Vivo Microdialysis in Pigs

Percutaneous Penetration Kinetics of Lidocaine and Prilocaine in Two Local Anesthetic Formulations Assessed by in Vivo Microdialysis in Pigs

Solubilization of Hydrophobic Guest Molecules in the Monoolein Discontinuous Q_L Cubic Mesophase and Its Soft Nanoparticles

Regional anesthesia with epinephrine‐containing lidocaine reduces pericatheter bleeding after tunneled hemodialysis catheter placement

Contact Info

Product

Resources

About

Physicochemical interaction of local anesthetics with lipid model systems—correlation with in vitro permeation and in vivo efficacy

Cited by 12 publications

References 23 publications

Percutaneous Penetration Kinetics of Lidocaine and Prilocaine in Two Local Anesthetic Formulations Assessed by in Vivo Microdialysis in Pigs

Percutaneous Penetration Kinetics of Lidocaine and Prilocaine in Two Local Anesthetic Formulations Assessed by in Vivo Microdialysis in Pigs

Solubilization of Hydrophobic Guest Molecules in the Monoolein Discontinuous QL Cubic Mesophase and Its Soft Nanoparticles

Regional anesthesia with epinephrine‐containing lidocaine reduces pericatheter bleeding after tunneled hemodialysis catheter placement

Contact Info

Product

Resources

About

Solubilization of Hydrophobic Guest Molecules in the Monoolein Discontinuous Q_L Cubic Mesophase and Its Soft Nanoparticles