Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol

The pharmacokinetics of some β-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre- and postoperative period of CABG with moderately hypothermic CPB (32°C). On the day before and on the first day after surgery, blood samples were collected before β-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 ± 0.75 to 11.46 ± 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 ± 2.83 to 19.33 ± 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 ± 1.60 to 11.44 ± 2.89 h) or atenolol volume of distribution (from 2.90 ± 0.36 to 3.83 ± 0.72 L/kg). Total clearance was not changed by surgery. These CPB-induced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery.

Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol.

The pharmacokinetics of some beta-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre- and postoperative period of CABG with moderately hypothermic CPB (32 degrees C). On the day before and on the first day after surgery, blood samples were collected before beta-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 +/- 0.75 to 11.46 +/- 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 +/- 2.83 to 19.33 +/- 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 +/- 1.60 to 11.44 +/- 2.89 h) or atenolol volume of distribution (from 2.90 +/- 0.36 to 3.83 +/- 0.72 L/kg). Total clearance was not changed by surgery. These CPB-induced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery.

Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery.

The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 +/- 8 years, mean weight 75.4 +/- 11.9 kg and mean body surface area 1.83 +/- 0.19 m(2)), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95% CI = 3.9-6.9) to 10.6 h (95% CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3) to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6) vs 10.7 ml min(-1) kg(-1) (95% CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery

The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m²), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95 percent CI = 3.9-6.9) to 10.6 h (95 percent CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95 percent CI = 3.2-14.3) to 8.3 l/kg (95 percent CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95 percent CI = 7.7-24.6) vs 10.7 ml min-1 kg-1 (95 percent CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

Systemic availability of prophylactic cefuroxime in patients submitted to coronary artery bypass grafting with cardiopulmonary bypass.

Cardiopulmonary bypass and hypothermia (HCPB) is a procedure commonly used during heart surgery, representing a risk factor for the patient by promoting extensive haemodilution and profound physiological changes. Cefuroxime is used for the prevention of infection following heart surgery, and several dose schemes have been suggested for prophylaxis with cefuroxime. The objective of the present study was to assess, in a comparative manner, the systemic availability of cefuroxime administered intravascularly as a bolus dose of 1.5 g to 17 patients having heart surgery with or without HCPB. Plasma cefuroxime concentrations were determined by high-pressure liquid chromatography-UV, and the following values, expressed as medians, were obtained for the study group compared with controls: 69.1 vs. 62.7 mg/L (1st h), 35.8 vs. 26.0mg/L (3rd h), 14.6 vs. 8.7 mg/L (6th h, P<0.05), 6.1 vs. 3.0mg/L (9th h, P<0.05) and 2.6 vs. 1.0mg/L (12th h, P<0.05). Despite the differences recorded during the study period as a consequence of HCPB, low antibiotic concentrations were found as early as 6h post dose for both groups investigated. Thus, the low systemic availability of cefuroxime after the administration of a 1.5-g dose may not protect against postoperative infections. The data obtained permit us to recommend a change in the dose scheme in order to maintain adequate plasma levels of cefuroxime.

A micromethod for quantitation of debrisoquine and 4-hydroxydebrisoquine in urine by liquid chromatography

We describe a new simple, selective and sensitive micromethod based on HPLC and fluorescence detection to measure debrisoquine (D) and 4-hydroxydebrisoquine (4-OHD) in urine for the investigation of xenobiotic metabolism by debrisoquine hydroxylase (CYP2D6). Four hundred µl of urine was required for the analysis of D and 4-OHD. Peaks were eluted at 8.3 min (4-OHD), 14.0 min (D) and 16.6 min for the internal standard, metoprolol (20 µg/ml). The 5-µm CN-reverse-phase column (Shimpack, 250 x 4.6 mm) was eluted with a mobile phase consisting of 0.25 M acetate buffer, pH 5.0, and acetonitrile (9:1, v/v) at 0.7 ml/min with detection at lexcitation = 210 nm and lemission = 290 nm. The method, validated on the basis of measurements of spiked urine, presented 3 ng/ml (D) and 6 ng/ml (4-OHD) sensitivity, 390-6240 ng/ml (D) and 750-12000 ng/ml (4-OHD) linearity, and 5.7/8.2 percent (D) and 5.3/8.2 percent (4-OHD) intra/interassay precision. The method was validated using urine of a healthy Caucasian volunteer who received one 10-mg tablet of Declinax®, po, in the morning after an overnight fast. Urine samples (diuresis of 4 or 6 h) were collected from zero to 24 h. The urinary excretion of D and 4-OHD, Fel (0-24 h), i.e., fraction of dose administered and excreted into urine, was 6.4 percent and 31.9 percent, respectively. The hydroxylation capacity index reported as metabolic ratio was 0.18 (D/4-OHD) for the person investigated and can be compared to reference limits of < 12.5 for poor metabolizers (PM) and < 12.5 for extensive metabolizers (EM). In parallel, the recovery ratio (RR), another hydroxylation capacity index, was 0.85 (4-OHD: SD + 4-OHD) versus reference limits of RR < 0.12 for PM and RR > 0.12 for EM. The healthy volunteer was considered to be an extensive metabolizer on the basis of the debrisoquine test.

Pharmacokinetics and pharmacodynamics of propranolol in hypertensive patients after sublingual administration: systemic availability

The bioavailability of propranolol depends on the degree of liver metabolism. Orally but not intravenously administered propranolol is heavily metabolized. In the present study we assessed the pharmacokinetics and pharmacodynamics of sublingual propranolol. Fourteen severely hypertensive patients (diastolic blood pressure (DBP) =115 mmHg), aged 40 to 66 years, were randomly chosen to receive a single dose of 40 mg propranolol hydrochloride by sublingual or peroral administration. Systolic (SBP) and diastolic (DBP) blood pressures, heart rate (HR) for pharmacodynamics and blood samples for noncompartmental pharmacokinetics were obtained at baseline and at 10,20,30,60 and 120 min after the single dose. Significant reductions in BP and HR were obtained, but differences in these parameters were not observed when sublingual and peroral administrations were compared as follows: SBP (17 vs 18 percent, P=NS), DBP (14 vs 8 percent, P=NS) and HR (22 vs 28 percent, P=NS), respectively. The pharmacokinetic parameters obtained after sublingual or peroral drug administration were: peak plasma concentration (CMAX): 147 + 72 vs 41 + 12 nl/ml, P<0.05; time to reach CMAX (TMAX): 34 + 18 vs 52 + 11 min, P<0.05; biological hall-life (t1/2b): 0.91 + 0.54 vs 2.41 + 1.16 h, P<0.05; area under the curve (AUCT): 245 + 134 vs 79 + 54 ng h(-1) ml(-1), P<0.05; total body clearance (CLT/F):44 + 23 vs 26 + 12 ml min(-1) kg(-1), P=NS. Systemic availability measured by the AUCT ratio indicates that extension of bioavailability was increased 3 times by the sublingual route. Mouth paresthesia was the main adverse effect observed after sublingual administration. Sublingual propranolol administration showed a better pharmacokinetic profile and this route of administration may be an alternative for intravenous or oral administration.

Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients submitted to myocardial revascularization and cardiopulmonary bypass (CPB), 3 females and 7 males aged 65 ñ 11 years, 74 ñ 16 kg body weight, 166 ñ 9 cm height and 1.80 ñ 0.2l m2 body surface area (BSA), and control, 14 surgical patients not submitted to CPB, 11 female and 3 males aged 41 ñ 14 years, 66 ñ 14 kg body weight, 159 ñ 9 cm height and 1.65 ñ 0.16 m2 BSA (mean ñ SD). Sodium diclofenac (1 mg/kg, im Voltaren 75( twice a day) was administered to patients in the Recovery Unit 48 h after surgery. Venous blood samples were collected during a period of 0-12 h and analgesia was measured by the visual analogue scale(VAS) during the same period. Plasma diclofenac levels were measured by high performance liquid chromatography. A two-compartment open model was applied to obtain the plasma decay curve and to estimate kinetic parameters. Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels were increased five-fold in CPB patients. Data obtained for analgesia reported as the maximum effect (EMA were: 25 per cent VAS (CPB) vs 1O per cent VAS (control), P<0.05, median measured by the visual analogue scale where lOO per cent is equivalent to the highest level of pain. To correlate the effect versus plasma diclofen levels, the EMAX sigmoid model was applied. A prolongation of the mean residence time for maximum effect (MRTEMAX) was observed without any change in lag-time in CPB in spite of the reduced analgesia reported for these patients, during the time-dose interval. In conclusion, the extent of plasma diclofenac protein binding was influenced by CPB with clinicall relevant kinetic-dynamic consequences.

A simple and sensitive high-performance liquid chromatographic method to measure antipyrine and its metabolites in human urine

A method which permits the simultaneous HPLC analysis of antipyrine (A), 3-hydroxymethylantipyrine (HMA), 4-hydroxyantipyrine (HOA) and norantiopyrine (NORA) using a single extraction step in a five minute chromatographic run is described. Only 500 micraLitro of urine were necessary for the quantitation of all compounds investigated. An analog derivative, 4-aminoantipyrine, was used as internal standard (IS). Urine samples were hydrolyzed with Limpet acetone powder, 37 graus centigrados, pH 5.0 for 2 h. Sodium chloride was added and urine samples were extracted with diclhormethane-isopropyl alcohol (90:10, v/v) in acidic medium. The residue was dissolved with mobile phase, washed with n-hexane and 20 micralitro of the lower phase were injected into a 4-micron Nova-Pak (R) 'C IND. 18' column. Peaks monitored at 254 nm were eluted with 0.75 M sodium acetate buffer, pH 5.0: methanol, (70:30, v/v) as mobile phase. The method, validated on the basis of the confidence limits for antipyrine and its metabolites, presented good stability, sensitivity, linearity, and intra or interassay precisions lower than 5 percente for all commpounds were investigated. This assay was applied for drug metabolism study carried out in ten healthy volunteers: 23 about 5 yr and 63 about 10 kg(mean about SD) after p.o. single dose of antipyrine, 500 mg/capsule. Diuresis of 24 h up to 72 h of drug administration was preserved with sodium metabisulfite, 4 mg/mL. Biological fluids were stored at -20 centigrade degree until assay. The main hydroxy-metabolites (HMA + HOA) and NORA, minor N-demethylated metabolite of antipyrine, were excreted: 60 percent and 20 percente as percentage of the given dose, respectively. Clearances for production of metabolites expressed as mL/min, were: 8.61 about 4.28 (7.24) for HMA, 13.91 about 6.20(12.67) for HOA, and 8.08 about 4.01(5.93) for NORA, mean about SD (median).

Theophylline-ranitidine interaction in elderly COPD patients

Most controlled studies in humans indicate that ranitidine does not alter theophylline metabolism, even at high doses. However, there have been several case reports published recently which demostrate the development of theophylline toxicity mostly in older patients receiving stable oral doses of this drug when ranitidine was administered simultaneously. We studied eleven elderly (mean age, 69,0 + or - 6.2 years) patients with chronic obstructive pulmonary disease (COPD). During one week the patients took slow-release theophylline, 200 mg every 12 h, followed by one week intake of the same dose of theophylline plus ranitidine tables, 150 mg every 12h. At the end of each period, blood samples were obtained 0,1,2,3,4,6,7,8 and 12h after the morning dose for the determination of serum theophylline levels. the peak theophylline concentration was achieved after 4.1 + or - 0.9 h while the patients were taking theophylline, and after 2.9 + or - 1.4 h with the combined regimen. This difference was statistically significant. These results suggest that the reported increases in serum theophylline levels in older patients receiving theophylline and ranitidine cannot be ascribed to slower theophylline metabolism in the geriatric patient with COPD who is also given ranitidine.

Simplified micromethod for the HPLC measurement of diclofenac in plasma

A simple and senmsitive micromethod based on HPLC is described for the measurement of diclofenac in 200 ul plasma. A single extraction with dichlormethane in acidic medium was an essential clean-up step. Diclofenac and its internal standard (cyclohexendiphenyl propionic acid) were eluted at 3.3 and 6.5 min from a 4-micron C18 reverse-phase column using a mobile phase consisting of 0.75 M sodium acetate buffer, pH 5.0, and acetonitrile (55:45, v/v) at a flow rate of 0.9 ml/min with detection at 282 nm. The method, validated on the basis of parameters evaluated nfor the confidence limits of diclofenac measurements in spiked plasma, presented 1 ng/ml sensitivity, 10-10,000 ng/ml linearity, and 3.5% and 5.7% intra-and interassay precision, respectively. Peak plasma diclofenac levels ranging from 177 to 841 ng/ml and from 276 to 1008 ng/ml were obtained for two slow-release formulations. A wide range (1 ng/ml-3 ug/ml) was observed for plasma diclofenac levels of volunteers during a 24-h study period

Influencia da associacao teofilina e beta-2-agonista por via oral, na funcao pulmonar de pacientes portadores de doenca pulmonar obstrutiva cronica / Influence of the combination of theophylline and beta 2 agonists by oral route on pulmonary function of patients with chronic obstructive lung disease

A eficacia da associacao de teofilina e agentes beta-adrenergicos na terapeutica da obstrucao bronquica e tema controverso na literatura. Com este objetivo, foram estudados nove pacientes portadores de DPOC, com idades entre 51 e 69 (media de 60,6 ñ 6,6) anos, nos quais foi comparada a funcao pulmonar com o uso de teofilina isolada ou combinada ao salbutamol, por via oral. Apos a suspensao de qualquer medicacao broncodilatadora por 24 horas foram determinados os valores basais da capacidade vital forcada (CVF) e do volume expiratorio forcado no primeiro segundo "(VEF IND. 1)". Teofilina de acao prolongada (600mg/dia) foi, entao, administrada por via oral por sete dias, seguidos de sete dias de ingestao oral na mesma dose de teofilina associada a 16mg/dia de salbutamol. Os parametros espirometricos foram analisados ao final de cada semana. A CVF basal foi de 0,85 e 2,57 (media 1,78 ñ 0,64) litros, o "VEF IND. 1" 0,70 a 164 (medida 1,15 ñ 0,30) litros e a teofinemia 0,1 a 3,1 (media 1,81 ñ 1,01) ug/ml. Ao final da primeira semana, a CVF foi de 1,38 a 3,26 (media 2,03 ñ 0,65) litros, o "VEF IND. 1" 0,85 a 1,73 (media 1,40 ñ 0,29) litros e os niveis sericos de teofilina 8,1 a 21,0 (media 13,40 ñ 4,18) ug/ml. Com a associacao teofilina e salbutamol a CVF encontra-se entre 1,24 e 2,57 (media 1,90 ñ 0,50) litros e o "VEF IND. 1" entre 0,96 e 1,90 ...

Efeitos dos agonistas beta-2-adrenergicos por via oral, sobre os niveis sericos de teofilina / Effects of adrenergic beta 2 agonists by oral route on theophylline blood levels

Diversas drogas interferem com a farmacocinetica da teofilina, acarretando variacoes de seus niveis sericos. Com o objetivo de caracterizar possiveis influencias dos beta-2-adrenergicos por via oral, na teofilinemia de pacientes em uso desta droga, analisamos dez portadores de obstrucao bronquica, com idades entre 51 a 69 (media de 59,90 ñ 6,67) anos. O estudo consistiu na analise da concentracao serica de teofilina 24 horas apos a suspensao de toda medicacao, depois de um periodo de administracao diaria isolada de 600 mg de teofilina de acao prolongada, e apos sete dias de associacao da mesma dose de teofilina com 16 mg diarios de salbutamol por via oral. As amostras sanguineas foram colhidas 4 horas apos a ingestao da dose matinal de teofilina. Os resultados obtidos foram respectivamente 2,08 ñ 1,20 ug/ml, 15,18 ñ 6,87 ug/ml e 11,45 ñ 5,15 ug/ml. Os valores da fase (teofilina isolada) foram significativamente maiores aos obtidos apos a combinacao de teofilina e salbutamol. Estes resultados permitem concluir que esta associacao por via oral interfere na farmacocinetica da teofilina. Sugerimos que nos individuos em uso destas drogas, os niveis de teofilina sejam monitorizados, para eventual correcao da dose administrada.

Farmacocinética da bupivacaína em anestesia peridural cesariana: II. Soluçöes a 0,5% com ou sem epinefrina / Pharmacokinetics of bupivacaine in epidural anesthesia for cesaren section: II. Solutions at 0,5% with of without epinephrine

A bupivacaína a 0,5% foi utilizada em anestesia peridural para cesariana na dose fixa de 150 mg, determinando-se as concentraçöes plasmáticas venosas maternas e os parâmetros farmacocinéticos do anestésico. Foram estudadas 20 gestantes de termo, submetidas à cesariana eletiva. Dez pacientes receberam 150 mg de bupivacaína a 0,5% com epinefrina 1:200.000 e 10 pacientes receberam 150 mg do mesmo anestésico sem epinefrina. As concentraçöes plasmáticas venosas de bupivacaína foram determinadas em diferentes tempos após sua injeçäo peridural, por meio de técnica em cromatografia gás-líquido. As concentraçöes plasmáticas nos diferentes tempos se mostraram sempre dentro de limites reconhecidamente seguros (valor máximo obtido 2,22 microng.ml-1), sendo sempre mais elevados no grupo que recebeu anestésico local sem epinefrina, embora essas diferenças näo tenham sido significativas. A concentraçäo plasmática máxima média foi significativamente reduzida no grupo com epinefrina (1,26 + ou - 0,20 microng.ml-1) quando comparado com o grupo sem epinefrina (1,51 + ou - 0,30 microng.ml-1); o tempo necessário para obtençäo da mesma foi coincidente nos dois grupos (20,50 + ou - 5,50 min). A quantidade total de anestésico transferida para o comportamento central e a meia vida de eliminaçäo do mesmo no grupo sem epinefrina (213,23 + ou - 76,38 microng.ml-1.min e 98,84 + ou - 40,69 min) näo foram significativamente diferentes dos obtidos no grupo com epinefrina (171,34 + ou - 52,80 microng.ml-1.min e 102,40 + ou - 35,25 min)

Farmacocinética da bupivacaína em anestesia peridural para cesariana: III. Estudo comparativo entre soluçöes a 0,5 e 0,75% / Pharmacokinetics of bupivacaine in epidural anesthesia for cesarean section. III. Comparative study of solutions at 0,5% and 0,75%

A bupivacaína a 0,5% ou 0,75% foi utilizada em anestesia peridural para cesariana na dose fixa de 150mg, determinando-se as concentraçöes plasmáticas venosas maternas e os parâmetros farmacocinéticos do anestésico. Foram estudadas 37 gestantes de termo, submetidas a cesariana eletiva, que receberam soluçöes de bupivacaína a 0,5% ou a 0,75%, com ou sem epinefrina 1:200.000. As concentraçöes plasmáticas do anestésico foram determinadas por meio de técnica em cromatografia gás-líquido. Na ausência de epinefrina, a quantidade total de droga transferida para o compartimento central e a meia vida de eliminaçäo da bupivacaína foram significativamente maiores no grupo que recebeu soluçöes a 0,75% (301,59 + ou - 80,50 microng.ml-1.min e 172,36 + ou - 33,90 min) quando comparado com o grupo que recebeu soluçöes a 0,5% (213,23 + ou - 76,38 microng.ml-1.min e 98,84 + ou - 40,69 min) (p<0,05) Na presença de epinefrina, näo se observaram diferenças significativas nas concentraçöes plasmáticas e nos parâmetros farmacocinéticos estudados, independente da utilizaçäo de soluçöes a 0,5% ou a 0,75%. A maior concentraçäo plasmática obtida em toda a investigaçäo foi de 2,22 microng.ml-1, após a utilizaçäo de bupivacaína a 0,5% sem epinefrina

Farmacocinética da bupivacaína a 0,75% em anestesia peridural para cesarianas: I. Soluçöes a 0,75% com e sem epinefrina / Pharmacokinetics of bupivacaine in epidural anesthesia for cesarean section: I. 0.75% solution with and without epinephrine

A bupivacaína a 0,75% foi utilizada em anestesia peridural para cesariana na dose fixa de 150 mg, determinando-se os níveis plasmáticos maternos e os parâmetros farmacocinéticos do anestésico. Foram estudadas 17 gestantes de termo, submetidas à cesariana eletiva. Dez pacientes receberam 150 mg de bupivacaína a 0,75% com epinefrina 1:200.000 e sete pacientes receberam 150 mg do mesmo anestésico sem epinefrina. Os níveis plasmáticos de bupivacaína foram determinados em diferentes tempos após sua injeçäo peridural, por meio de técnica em cromatografia gás-líquido. Os níveis plasmáticos nos diferentes tempos se mostraram sempre dentro de limites reconhecidamente seguros (nível máximo obtido 2,00 microng/ml), sendo sempre mais elevados no grupo que recebeu anestésico local sem epinefrina, embora essas diferenças näo tenham sido significativas. O tempo para a obtençäo de pico plasmático e a concentraçäo de pico no grupo sem epinefrina (21,00 + ou - 6,73 min e 1,45 + ou - 0,40 microng/ml) näo foram diferentes dos obtidos para o grupo com epinefrina (23,90 + ou - 6,09 min e 1,32 + ou - 0,35 microng/ml). A meia vida de eliminaçäo do anestésico foi significativamente maior no grupo sem epinefrina (172,36 + ou - 33,90 min) do que no grupo com epinefrina (116,63 + ou - 57,03 min) (p < 0,05); da mesma forma a quantidade total de anestésico transferida para o compartimento central foi significativamente maior no grupo sem epinefrina (301,59 + ou - 80,05 microng.ml**-1.min) do que no grupo com epinefrina (217,28 + ou - 105,57 microng.ml**-1.min)