Spinal anaesthesia with Chloroprocaine HCl 1% for elective lower limb procedures of short duration: a prospective, randomised, observer-blind study in adult patients.

BACKGROUND: This prospective, randomised, observer-blinded study has been conducted in patients undergoing procedures of the lower extremities to evaluate the time to complete block resolution of 2-chloroprocaine 1% at three intrathecal doses (30, 40 and 50 mg). METHODS: After informed consent, we enrolled 45 male and female patients, aged 18-65 years, ASA score I-II, BMI 18-32 kg/m2, undergoing elective lower limb procedures lasting ≤40 min and with a requested dermatomeric level of sensory block ≥ T12. The patients were randomised in a 1:1:1 ratio to receive Chloroprocaine HCl 1% at one of the three different intrathecal doses (Group 30 = 30 mg, Group 40 = 40 mg or Group 50 = 50 mg). The progression and regression of both sensory and motor blocks were evaluated blindly. Urine and venous blood samples were collected for pharmacokinetic analysis. RESULTS: Times to regression of spinal blocks were 1.76 ± 0.35 h, 2.13 ± 0.46 h and 2.23 ± 0.38 h, in Group 30, 40 and 50 respectively: the 30 mg dose showed a significantly faster resolution of spinal block than the 40 mg (p = 0.034) and the 50 mg (p = 0.006). Time to readiness for surgery was significantly reduced with the dose of 50 mg when compared to dose of 30 mg (p = 0.0259). CONCLUSIONS: The doses of 50 mg and 40 mg yielded a longer resolution of spinal block than the dose of 30 mg. Nevertheless, the dose of 30 mg resulted in a higher secondary failure rate. TRIAL REGISTRATION: Registration of clinical trial: clinicaltrials.gov ( NCT02481505 ).

Does spinal chloroprocaine pharmacokinetic profile actually translate into a clinical advantage in terms of clinical outcomes when compared to low-dose spinal bupivacaine? A systematic review and meta-analysis.

STUDY OBJECTIVE: Spinal anesthesia is well suited for day-care surgery, however a persisting motor block after surgery can delay discharge. Among the new drugs available, chloroprocaine has been associated with a short onset time, and motor block duration and a quicker discharge. However, it is not clear if those outcomes are clinically significantly superior compared to those associated with the use of low-dose hyperbaric bupivacaine. DESIGN: Aim of the study was to determine if spinal 2-chloroprocaine was superior to low-dose spinal bupivacaine regarding the following outcomes: onset time, block duration, time to ambulation and time to discharge. PATIENTS/INTERVENTIONS: We performed a systematic literature search of the last 30 years using PubMed Embase and the Cochrane Controlled Trials Register. We included only blinded, prospective trials comparing chloroprocaine with a low dose of bupivacaine for spinal anesthesia. Low dose bupivacaine was defined as a dose of 10 mg or less. Outcomes of interest were time to motor block regression (primary outcome), time to ambulation and time to discharge (secondary outcomes), as indirect indicators of a complete recovery after spinal anesthesia. MAIN RESULTS: Compared to a low dose bupivacaine, spinal 2-chloroprocaine was associated with significantly faster motor and sensory block regression (pMD = -57 min-140.3 min; P = 0.015 and <0.001 respectively), a significantly shorter time to ambulation and an earlier discharge (pMD = -84.6 min; P < 0.001 and pMD = -88.6 min and <0.001 respectively). Onset time did not differ between the two drugs (pMD = -1.1 min; P = 0.118). CONCLUSIONS: Spinal 2-chloroprocaine has a shorter motor block duration, a significantly quicker time to ambulation and time to discharge compared to low dose hyperbaric bupivacaine and may be advantageous when spinal anesthesia is performed for day case surgery.

Confocal Raman microscopic investigation of the effectiveness of penetration enhancers for procaine delivery to the skin.

A methodology that employs confocal Raman microscopy (CRM) on ex vivo skin samples is proposed for the investigation of drug content and distribution in the skin. To this end, the influence of the penetration enhancers propylene glycol and polyoxyethylene-23-lauryl ether on the penetration and permeation of procaine as a model substance was investigated. The drug content of skin samples that had been incubated with semisolid formulations containing one of these enhancers was examined after skin segmentation. The experiments showed that propylene glycol did not affect the procaine content that was delivered to the skin, whereas polyoxyethylene-23-lauryl ether led to higher procaine contents and deeper penetration. Neither substance was found to influence the permeation rate of procaine. It is thereby shown that CRM can provide additional information on drug penetration and permeation. Furthermore, the method was found to enhance the depth from which Raman spectra can be collected and to improve the depth resolution compared to previously proposed methods.

Intrathecal 1% 2-chloroprocaine vs. 0.5% bupivacaine in ambulatory surgery: a prospective, observer-blinded, randomised, controlled trial.

BACKGROUND: This prospective, observer-blinded, randomised, multicentre study aimed at determining the non-inferiority of 50 mg of plain 1% 2-chloroprocaine vs. 10 mg of 0.5% plain bupivacaine in terms of sensory block onset time at T10 after spinal injection. The study hypothesis was that the difference in onset times of sensory block to T10 between the two drugs is ≤ 4 min. METHODS: One hundred and thirty patients undergoing lower abdominal or lower limb procedures (≤ 40 min) were randomised to receive one of two treatments: 50 mg of plain 1% 2-chloroprocaine (Group C, n = 66) or 10 mg of plain 0.5% bupivacaine (Group B, n = 64). Times to sensory and motor block onsets, maximum sensory block level, readiness for surgery, regression of sensory and motor blocks, first analgesic requirements, unassisted ambulation, home discharge, and side effects after 24 h and 7 days were registered blindly. RESULTS: Chloroprocaine was comparable with plain 0.5% bupivacaine in terms of time to sensory block at T10 level. Group C showed faster onsets of motor block (5 vs. 6 min), maximum sensory block level (8.5 vs. 14 min), resolution of sensory (105 vs. 225 min) and motor (100 vs. 210 min) blocks, unassisted ambulation (142.5 vs. 290.5 min), first analgesic requirement (120 vs. 293.5 min), and home discharge (150 vs. 325 min) (all comparisons, P < 0.05). No chloroprocaine patient developed transient neurological symptoms. CONCLUSION: Spinal anaesthesia with 50 mg of plain 1% 2-chloroprocaine is similar to 10 mg of plain 0.5% bupivacaine in terms of onset of sensory block at T10 but shows quicker recovery from anaesthesia than with 0.5% bupivacaine.

Lipophilicity as a determinant of binding of procaine analogs to rat α3ß4 nicotinic acetylcholine receptor.

Nicotinic acetylcholine receptors (nAChRs) have been studied in detail with regard to their interaction with therapeutic and drug addiction-related compounds. Using a structure-activity approach, we have examined the relationship among the molecular features of a set of eight para-R-substituted N,N-[(dimethylamino)ethyl] benzoate hydrochlorides, structurally related to procaine and their affinity for the α(3)ß(4) nAChR heterologously expressed in KXα3ß4R2 cells. Affinity values (log[1/IC50]) of these compounds for the α(3)ß(4) nAChR were determined by their competition with [(3)H]TCP binding. Log(1/IC50) values were analyzed considering different hydrophobic and electronic parameters and those related to molar refractivity. These have been experimentally determined or were taken from published literature. In accordance with literature observations, the generated cross-validated quantitative structure-activity relationship (QSAR) equations indicated a significant contribution of hydrophobic term to binding affinity of procaine analogs to the receptor and predicted affinity values for several local anesthetics (LAs) sets taken from the literature. The predicted values by using the QSAR model correlated well with the published values both for neuronal and for electroplaque nAChRs. Our work also reveals the general structure features of LAs that are important for interaction with nAChRs as well as the structural modifications that could be made to enhance binding affinity.

The interaction between epidural 2-chloroprocaine and morphine: a randomized controlled trial of the effect of drug administration timing on the efficacy of morphine analgesia.

BACKGROUND: The efficacy and duration of epidural morphine analgesia is diminished when administered after 2-chloroprocaine compared with lidocaine. The mechanism of the interaction between 2-chloroprocaine and morphine is unknown. Possible explanations include differences in the latency and duration of action of the two drugs or opioid receptor antagonism. We hypothesized that administration of epidural morphine 30 min before the initiation of 2-chloroprocaine anesthesia would result in postoperative analgesia of similar duration and quality to that achieved by epidural morphine after the initiation of lidocaine anesthesia in patients undergoing postpartum tubal ligation. METHODS: Subjects undergoing bilateral postpartum tubal ligation after vaginal delivery with epidural analgesia were randomized to one of three groups. Subjects received epidural morphine or saline 30 min before the initiation of analgesia with 3% 2-chloroprocaine (two groups) or 2% lidocaine (one group), and at the time of surgical incision, they received either epidural saline or morphine. The duration of analgesia was defined as the time from morphine administration until the first request for supplemental analgesia. Duration of epidural morphine analgesia was compared among groups using Kaplan-Meier survival analysis and the log-rank test. RESULTS: Administration of epidural morphine 30 min before the initiation of 2-chloroprocaine anesthesia (n = 29) resulted in a longer median duration of analgesia (28.6 h [95% CI 4.4-52.7]) compared with the administration of morphine after 2-chloroprocaine anesthesia (n = 30) (2.2 h [95% CI 0-4.8]) (P = 0.006). The median duration of analgesia observed when morphine was administered before 2-chloroprocaine was similar to that observed when morphine was administered after initiation of lidocaine anesthesia (n = 28) (25.8 h [95% CI 10.7-40.9]) (P = 0.83). Pain scores were not different in the postanesthesia care unit, but were higher on admission to the postpartum unit in the subjects receiving morphine after 2-chloroprocaine. Supplemental morphine equivalents administered in the first 48 h were similar among groups and there were no differences in opioid-related side effects. DISCUSSION: This study demonstrates that administration of epidural morphine 30 min before epidural anesthesia with 2-chloroprocaine provides a similar duration of analgesia as epidural morphine after epidural lidocaine anesthesia. This suggests that the observed interaction between epidural morphine and 2-chloroprocaine is a result of differences in latency and duration of action of the two drugs, or that the administration of morphine before 2-chloroprocaine effectively blocks a receptor site antagonism.

Specificity of procaine and ester hydrolysis by human, minipig, and rat skin and liver.

The capacity of human, minipig, and rat skin and liver subcellular fractions to hydrolyze the anesthetic ester procaine was compared with carboxylesterase substrates 4-methylumbelliferyl-acetate, phenylvalerate, and para-nitrophenylacetate and the arylesterase substrate phenylacetate. Rates of procaine hydrolysis by minipig and human skin microsomal and cytosolic fractions were similar, with rat displaying higher activity. Loperamide inhibited procaine hydrolysis by human skin, suggesting involvement of human carboxylesterase hCE2. The esterase activity and inhibition profiles in the skin were similar for minipig and human, whereas rat had a higher capacity to metabolize esters and a different inhibition profile. Minipig and human liver and skin esterase activity was inhibited principally by paraoxon and bis-nitrophenyl phosphate, classical carboxylesterase inhibitors. Rat skin and liver esterase activity was inhibited additionally by phenylmethylsulfonyl fluoride and the arylesterase inhibitor mercuric chloride, indicating a different esterase profile. These results have highlighted the potential of skin to hydrolyze procaine following topical application, which possibly limits its pharmacological effect. Skin from minipig used as an animal model for assessing transdermal drug preparations had similar capacity to hydrolyze esters to human skin.

The quantitation of procaine in equine plasma by liquid chromatography-linear ion trap mass spectrometry.

A method for the extraction and quantitation of procaine in equine plasma was developed for use with liquid chromatography-mass spectrometry (LC-MS). Procaine was isolated from equine plasma by liquid-liquid extraction at pH 11 with dichloromethane using procaine-d10 as an internal standard. Quantitation was achieved by LC-MS using a 3-microm C-18 column coupled to an electrospray ionization source on a linear ion-trap mass spectrometer. The limit of detection and limit of quantitation was determined to be 50 and 200 pg/mL, respectively. The lowest limit of detection determined by previous methods was 1 ng/mL. Administration samples were obtained as part of a larger study to determine a regulatory limit for procaine in racehorses and procaine concentrations were determined using this method.

Application of drug selective electrode in the drug release study of pH-responsive microgels.

The colloidal phenomenon of soft particles is becoming an important field of research due to the growing interest in using polymeric system in drug delivery. Previous studies have focused on techniques that require intermediate process step such as dialysis or centrifugation, which introduces additional errors in obtaining the diffusion kinetic data. In this study, a drug selective electrode was used to directly measure the concentration of procaine hydrochloride (PrHy) released from methacrylic acid-ethyl acrylate (MAA-EA) microgel, thereby eliminating the intermediate process step. PrHy selective membrane constructed using a modified poly (vinyl chloride) (PVC) membrane and poly (ethylene-co-vinyl acetate-co-carbon monoxide) as plasticizer exhibited excellent reproducibility and stability. The response was reproducible at pH of between 3 to 8.5 and the selectivity coefficients against various organic and inorganic cations were evaluated. Drug release was conducted using the drug electrode under different pHs and the release rate increased with pH. The release behavior of the system under different pH exhibited obvious gradient release characteristics.

Transplacental passage of Pt after treatment with the new triamine complex cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N4]-chloride platinum (II) monohydrochloride monohydrate.

Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N4]-chloride platinum (II) monohydrochloride monohydrate (DPR) is a monofunctional Pt triamine complex synthesized starting from cisplatin and procaine hydrochloride, characterized by a good antitumor activity coupled with low toxic effects and able to impair prenatal development of mice but at doses outside or just in the upper range of therapeutic doses. In the present paper the transplacental passage of DPR-derived Pt was investigated in CD1 mice on days 9, 13, 16 and 18 of pregnancy, 24 h after ip administration of 21 mg/kg DPR. For comparison, groups of mice were treated with an equivalent Pt-containing dose of cisplatin (10.7 mg/kg). Similarly to cisplatin, small amounts of Pt were detected in fetuses on day 9. From day 13 of gestation the concentration of DPR- and cisplatin-derived Pt increased up to the highest fetal concentrations detected on day 16. On day 18 the concentration of Pt decreased. Most importantly, on days 13-18 of pregnancy cisplatin-derived Pt was always significantly higher than that assayed after DPR administration. In addition, on day 13 of pregnancy Pt exposure of fetuses was significantly higher when dams were treated with cisplatin (AUC(0.5-24)= 3.40 vs. 4.95 microg.h/g). Finally, it is worth noting that serum decay of Pt after DPR or cisplatin administration in adult female mice was similar with AUC0.13-2h s of 7.5 and 6.6 microg.h/ml, respectively. When we determined the concentration of Pt into the main organs of fetuses from dams treated with either DPR or cisplatin on day 18 of gestation, we observed a different organ distribution. In fact, while the concentration of DPR-derived Pt was greater in the heart (1.08+/-0.30 vs. 0.78 +/- 0.35 microg/g, p <0.10), an opposite situation was found in the kidney (0.51+/-0.20 vs. 0.69 +/- 0.22 microg/g, p <0.05). In conclusion, our data show that DPR may pass through the placenta with an efficiency significantly lower than that of cisplatin. This finding may represent one of the possible causes of the lower embryotoxic/teratogenic effect of DPR as compared to cisplatin.

Programa de simulación farmacocinética para computadoras manuales / Farmacokinetic simulation software for handheld computers

Se ha desarrollado un programa de simulación farmacocinética, CINETICAPALM, que realiza la predicci¢n de la concentraci¢n en tiempo real de un fármaco en el plasma y en sitio-efecto, que corre en computadoras manuales de tipo Palm. CINETICAPALM permite simular la administración de fármacos en bolo e infusiones a velocidad constante, tanto por métodos gravimétricos como por bombas de infusión. El usuario simula la administración de un fármaco utilizando una base de datos con sus parámetros cinéticos. El programa predice la concentración en plasma y en sitio-efecto de un paciente determinado, mostrándola en tiempo real en forma numérica y gráfica. La versión actual de CINETICAPALM tiene en su base de datos los parámetros cinéticos de propofol, fentanilo, midazolan, remifentanilo, ketamina y procaína. Su funcionamiento fue comparado con el programa para computadoras personales de simulación y control de bombas de infusión para administrar fármacos intravenosos, STANPUMP, de dominio público. Los resultados indican que CINETICAPALM es una herramienta válida para la predicci¢n del comportamiento farmacocinético de los fármacos modelizados. Este desarrollo se presenta como un recurso innovador para el aprendizaje de las propiedades farmacocinéticas de los anestésicos y puede ser utilizado como guía para la administración de los mismos.

Determination of the stability of drugs in plasma.

In order for a drug to be effective, enough of the active form must reach the target to elicit the desired effect. The first-pass effect for drugs taken orally is well known but the metabolism of drugs in plasma must also be considered during the drug discovery and development process. For instance, hydrolysis of a compound by plasma enzymes can significantly alter the bioavailability of the active compound. This unit describes methods for the determination of the stability of compounds in plasma.

Pharmacological and toxicological aspects of combination of beta-lactam and aminoglycoside antibiotic, prednisolone and procaine hydrochloride on the example of Vetramycin.

Vetramycin is an injectable veterinary compound for animal use only. In veterinary medicine, it has been used for a long time as a bactericidal beta-lactam and aminglycoside antibiotics combination, extending the bactericidal spectrum of these substances. This compound, in addition to bactericidal procaine penicillin and dihydrostreptomycin (DHS), contains also prednisolone acetate and procaine hydrochloride, two biologically active substances. Prednisolone, a glucocorticoide, has an antiinflammatory, antiallergic, antiitchical and analgesic effect. Procaine hydrochloride, in turn, has a local anaesthetic effect and attenuates pain caused by irritable properties of antibiotics at the injection sites. The average dosage of, respectively, procaine benzylpenicillin (I.U./kg(-1) b.w.), DHS (microg/kg(-1) b.w.), prednisolone acetate (microg/kg(-1) b.w.) and procaine hydrochloride (mg/kg(-1) b.w.) in horses, cattle, pigs is 6000-15000, 10-11, 0.24-0.6 and 1.2-3.0; s.i.d., in sheep, foals, calves, piglets is 20000-40000, 10, 0.8-1.6 and 4-8; s.i.d., in dogs and cats is 30000-200000, 10, 0.8-1.6 and 4-8; s.i.d.. Intramammary injection dose (Vetramycin antimastitis ointment in syringe) in cows is 1000000 I.U. of procaine benzylpenicillin + 1000000 I.U. of dihydrostreptycin sulphate per quarter of udder, s.i.d., during 3 successive days.

[Magnetically-guided anesthetics based on highly dispersed iron powders coated by polyacrylamide]. / Magnitoupravliaemye anestetiki na osnove vysokodispersnykh poroshkov zheleza s poliakrilamidnym pokrytiem.

The effect of external magnetic field (direct and alternating) on the targeted delivery and distribution in body tissues of experimental animals of anesthetics (novocain, lidocaine, and trimecaine) immobilized on highly dispersed ferromagnetics with biocompatible coating was studied by the method of emission spectral analysis. The results are compared with the results obtained earlier on highly dispersed iron powders with dextran coating. The parameters for the powders with dextran coating are considerably lower than those for the magnetic carriers with the polyacrylamide coating.

Minimal blocking concentrations of bupivacaine and procaine in an exclusively nociceptive system in humans.

BACKGROUND AND OBJECTIVES: Prior to this investigation, there was no approach to compare both the potency of local anesthetics and their time course of action in a reproducible nociceptive system in humans. We tested whether the vascularly isolated vein segment is appropriate for such an approach. METHODS: In six healthy men, a hand vein segment was vascularly isolated and intraluminally stimulated with electropulses of constant current intensity. The subjects rated pain between threshold and maximally tolerable pain on a visual analogue scale. For determining minimal blocking concentrations (a measure of potency), the vein segment was continuously perfused with Tyrode's solution with increasing concentrations of bupivacaine or procaine for at least 10 minutes each until pain was completely blocked. Subsequently, the respective local anesthetic was rinsed off with Tyrode's solution to determine the time course of recovery. RESULTS: Both bupivacaine and procaine blocked pain in a concentration-related fashion, the minimal blocking concentrations being 1.6 (0.6-1.9; median and range) mmol/L for bupivacaine and 15.0 (7.5-22.5) mmol/L for procaine. Whereas the onset of block (time of 50% block) did not differ significantly between bupivacaine and procaine [43 s (range, 3-80) vs 53 s (range, 30-115)], local anesthesia lasted significantly longer after application of bupivacaine [278 s (range, 215-325)] than after procaine [183 s (range, 125-225)]. CONCLUSIONS: The vascularly isolated vein segment is well suited to compare in vivo the properties of local anesthetics with a minimally invasive approach at a reproducible nociceptive system in humans.

Interacción entre relajantes musculares y fármacos usados en anestesia intravenosa / Interaction between muscle relaxants and drugs used in intravenous anesthesia

Los fármacos usados en anestesia general intravenosa tienen estructura química muy diferente entre sí, y la interacción de los relajantes musculares con ellos no es la misma. El tiopental sódico, los opiáceos y el propofol no manifiestan interacción con los relajantes no despolarizantes o la succinilcolina, salvo condiciones especiales con esta última droga. Las benzodiazepinas pueden prolongar el bloqueo neuromuscular por galamina y aumentar la potencia del vecuronio (desvío de la curva dosis-respuesta a la izquierda), pero sin magnitud importante de la interacción, mientras pueden disminuir ligeramente la magnitud de las fasciculaciones musculares por succinilcolina. La ketamina puede prolongar tanto el bloqueo despolarizante como no despolarizante, sin afectar el potencial de membrana, aunque interfiere con las corrientes propias de los potenciales de acción de la sinapsis y músculo. A dosis menores aumenta la fuerza muscular en forma directa. La procaína administrada por infusión intravenosa es el fármaco de mayores interacciones con los relajantes musculares. Prolonga la duración de la succinilcolina por competencia enzimática, inhibe las fasciculaciones, no modifica los tiempos de presentación de la taquifilaxia y el bloqueo Fase II y III, pero disminuye las dosis acumuladas del relajante necesarias para dichos fenómenos. Su comportamiento en el bloqueo no despolarizante es variable dependiendo de cual sea el relajante. Disminuye la DE50 de la d-tubocurarina. Modifica las pendientes de las curvas dosis-respuesta a la d-tubocurarina y galamina inclinándolas a la izquierda. Demora la fase inicial de recuperación (Duración Clínica) de la galamina y pancuronio, así como su índice de Recuperación. También disminuye la actividad de la butirilcolinestarasa, más con el pancuronio que con los demás, y no tiene interacción alguna con el alcuronio. Las interacciones con los relajantes de duración intermedia o corta, si se presentan, son de menor magnitud.

Quantification of penicillin-G and procaine in equine urine and plasma using high-performance liquid chromatography.

A rapid and sensitive method for the extraction and quantification of penicillin-G and procaine in horse urine and plasma samples has been successfully developed. The method involves the use of solid-phase extraction (SPE) for penicillin-G, liquid-liquid extraction (LLE) for procaine, and high-performance liquid chromatography (HPLC) for the quantification of penicillin-G and procaine. The new method described here has been successfully applied in the pharmacokinetic studies of procaine, penicillin-G and procaine-penicillin-G administrations in the horse.

The effects of extracellular pH with and without bicarbonate on intracellular procaine concentrations and anesthetic effects in crayfish giant axons.

BACKGROUND: The potentiating effect of sodium bicarbonate on local anesthetic action is attributed to two mechanisms: (1) an increase in the un-ionized local anesthetic due to extracellular alkalinization, and (2) an accelerated conversion of local anesthetic from un-ionized to ionized form with intracellular acidification caused by bicarbonate. To evaluate these hypotheses, the intracellular pH, intracellular ionized procaine concentration, and evoked action potentials were measured in crayfish giant axons. METHODS: In all measurements, axon preparations from crayfish were perfused extracellularly for 15 min with either bicarbonate-containing solution at pH 7.6 (bicarb/7.6) or bicarbonate-free solution at pH 7.6 (nonbicarb/7.6) or pH 8.0 (nonbicarb/8.0). Intracellular pH was measured using a pH-sensitive microelectrode. Intracellular anesthetic concentration was measured using a specially designed procaine-sensitive microelectrode with each of three solutions containing 1 mM procaine hydrochloride. Membrane potential was measured and, as an index of anesthetic action, the dV/dt of evoked action potential was calculated during perfusion with procaine. RESULTS: Mean intracellular pH was significantly lower in the bicarb/7.6 (7.16+/-0.07) group than in the nonbicarb/7.6 (7.33+/-0.09) and nonbicarb/8.0 (7.33+/-0.12) groups (P < 0.01). The mean intracellular ionized procaine concentration was significantly higher in the bicarb/7.6 (0.53+/-0.08 mM; P < 0.05) and nonbicarb/8.0 (0.58+/-0.13 mM; P < 0.01) than in nonbicarb/7.6 (0.32+/-0.14 mM) group but did not differ between the bicarb/7.6 and nonbicarb/8.0 groups. The mean percentage decrease in dV/dtmax was approximately coincident with the mean intracellular procaine concentration in each solution. CONCLUSION: The presence of bicarbonate or extracellular alkalinization increased the intracellular concentration of ionized procaine and the anesthetic effect.

Possibilities of conveying a cationic drug in Carbomer hydrogels.

A drug with cationic characteristics such as procaine can be conveyed in a Carbomer hydrogel in two different ways: (i) in the form of salt in solution in the aqueous phase, and (ii) in the base form salified with the same polymer. Introduction of the drug into the hydrogel with different concentrations of polymer produced, in both cases, a reduction in viscosity in relation to drug concentration. The gels with procaine salified with the polymer showed greater viscosity. The drug release rate, in general, diminished with the increase in polymer concentration. Nevertheless, when this concentration was maintained, there was no variation in release rate when the viscosity produced as a consequence of drug concentration was changed. Gels with procaine salified with the carboxyvinylic polymer had a faster release rate than those with procaine in the hydrochloride form dissolved in the aqueous phase. These results have also been confirmed by a simulated absorption test.