[Prescription errors in chemotherapy]. / Errores de prescripción en quimioterapia.

OBJECTIVE: To describe and analyse the role of the pharmacy department in detecting errors in the prescription of cytostatic drugs. METHOD: A retrospective study was carried out over a two year period (2003-2004), which reviewed the errors detected by pharmacists in chemotherapy prescriptions. Medication errors were classified according to the system published by Otero et al. in the paper OErrores de medicaci-n: estandarizaci-n de la terminolog a y clasificaci-nO (Medication errors: standardizing the terminology and taxonomy). RESULTS: During the period analysed, 43,188 doses of parenteral cytostatic drugs were prepared for the treatment of 3,959 patients. A total of 135 errors were detected (3.1/1,000 preparations). Errors were distributed as follows: incorrect dose (38.5%), drug omission (21.5%), incorrect drug (11.1%), frequency error and incorrect treatment duration (9.6% each), incorrect patient (7.4%), incorrect administration rate (1.5%) and incorrect administration route (0.7%). All of the errors would be classified with a B level of seriousness, since they were resolved in the pharmacy department before dispensing the drugs. At least 66 of these could be classified as potential adverse drug events. Furthermore, 11 cases of incorrect reductions in doses and 12 cases of omissions of cytostatic drugs were detected and these errors could lead to a possible reduced treatment efficiency. CONCLUSIONS: Despite the low incidence of errors detected in chemotherapy prescriptions, their potential seriousness gives the pharmaceutical validation process a key role in improving safety for patients.

Errores de prescripción en quimioterapia / No disponible

Objetivo: Describir y analizar la contribución del servicio de farmacia en la detección de errores en la prescripción de tratamientos citostáticos. Método: Se realizó un estudio retrospectivo, revisando los errores detectados por el farmacéutico en las prescripciones de quimioterapia recibidas durante los años 2003 y 2004. Para la clasificación de los errores de medicación detectados se utilizó la taxonomía publicada por Otero y cols., recogida en el documento “Errores de medicación: estandarización de la terminología y clasificación”. Resultados: Durante el periodo estudiado se han preparado en nuestro servicio 43.188 dosis de citostáticos parenterales, para 3.959 pacientes. El número total de errores detectados ha sido de 135 (3,1/1.000 preparaciones). La distribución de los errores es la siguiente: dosis incorrecta 38,5%, omisión de medicamento 21,5%, medicamento erróneo 11,1%, frecuencia errónea y duración incorrecta 9,6% cada uno, paciente erróneo 7,4%, velocidad de administración incorrecta 1,5% y vía de administración incorrecta 0,7%. Todos los errores se clasificarían como categoría de gravedad B, ya que se solventaron en el servicio de farmacia antes de dispensar los medicamentos. Destacar que al menos 66 de ellos podrían clasificarse como acontecimiento adverso potencial. Señalar también que en 11 casos se detectaron reducciones erróneas de dosis y en 12 omisiones de citostáticos, lo que conlleva una posible disminución de eficacia terapéutica. Conclusiones: A pesar de la baja incidencia de errores detectados en la prescripción de quimioterapia, la gravedad potencial de los mismos convierte el proceso de validación farmacéutica en un punto clave para mejorar la seguridad del paciente

Objective: To describe and analyse the role of the pharmacy department in detecting errors in the prescription of cytostatic drugs. Method: A retrospective study was carried out over a two year period (2003-2004), which reviewed the errors detected by pharmacists in chemotherapy prescriptions. Medication errors were classified according to the system published by Otero et al. in the paper “Errores de medicación: estandarización de la terminología y clasificación” (Medication errors: standardizing the terminology and taxonomy). Results: During the period analysed, 43,188 doses of parenteral cytostatic drugs were prepared for the treatment of 3,959 patients. A total of 135 errors were detected (3.1/1,000 preparations). Errors were distributed as follows: incorrect dose (38.5%), drug omission (21.5%), incorrect drug (11.1%), frequency error and incorrect treatment duration (9.6% each), incorrect patient (7.4%), incorrect administration rate (1.5%) and incorrect administration route (0.7%). All of the errors would be classified with a B level of seriousness, since they were resolved in the pharmacy department before dispensing the drugs. At least 66 of these could be classified as potential adverse drug events. Furthermore, 11 cases of incorrect reductions in doses and 12 cases of omissions of cytostatic drugs were detected and these errors could lead to a possible reduced treatment efficiency. Conclusions: Despite the low incidence of errors detected in chemotherapy prescriptions, their potential seriousness gives the pharmaceutical validation process a key role in improving safety for patients

Stability of moxifloxacin injection in peritoneal dialysis solution bags (Dianeal PD1 1.36% and Dianeal PD1 3.86%).

BACKGROUND AND OBJECTIVE: Moxifloxacin is a new fluorquinolone with broad-spectrum activity. It is suitable for treating peritonitis in peritoneal dialysis (PD) patients. The objective of this study was to test stability of moxifloxacin in PD solutions stored at different temperatures. METHODS: Dialysis solution bags were used at two glucose concentrations; Dianeal PD1 1.36% and Dianeal PD1 3.86%. Moxifloxacin solution (2%) was injected into nine 2-L bags of Dianeal PD1 1.36% and nine bags of Dianeal PD1 3.86% under aseptic conditions to achieve a nominal concentration of 25 mg/L. Three bags of Dianeal PD1 1.36% and three bags of Dianeal PD1 3.86% were stored at each of three temperatures (4, 25 and 37 degrees C) and the same way for. Duplicate samples (2 mL) were taken at different times and precipitation, cloudiness, colour and pH was analysed. Moxifloxacin concentrations were measured using a modified HPLC method. RESULTS: The mean moxifloxacin concentration in the Dianeal PD1 1.36% solution remained > or =90% of the initial concentration for 14 days at 4 degrees C, 7 days at 25 degrees C and 3 days at 37 degrees C. For Dianeal PD1 3.86% moxifloxacin concentrations remained > or =90% for 14 days at 4 degrees C, 3 days at 25 degrees C and 12 h at 37 degrees C. CONCLUSIONS: Moxifloxacin shows sufficient stability in both PD bags for use in PD patients.

Pharmacokinetics and tissue tolerance of azithromycin after intramuscular administration to rabbits.

The pharmacokinetics of azithromycin after intravenous and intramuscular injection at a single dose rate of 10mg/kg bodyweight were investigated in rabbits by using a modified agar diffusion bioassay for determining plasma concentrations. The plasma creatine kinase activity was determined after i.m. administration for the evaluation of the tissue tolerance. The elimination half-lives of azithromycin after intravenous and intramuscular administration were 24.1 and 25.1h, respectively. After intramuscular administration mean peak plasma concentration was 0.26+/-0.01 mg/L and bioavailability was 97.7%. Plasma CK activity rose sharply within 8h after i.m. injection of azithromycin; activity returned to pre-treatment level by 48-72 h post-treatment. The transient rise in serum CK activity indicates some degree of muscle tissue damage at the injection site.

Mejora de la calidad del proceso de llenado de carros de medicación en un sistema de distribución de medicamentos en dosis unitarias / Quality improvement of filling medication tolleys process for an unit-dose drug distribution system

Objetivo: Evaluar la calidad del proceso de llenado de carrosen un sistema de distribución en dosis unitarias tras la implantaciónde un protocolo.Método: Se definieron cinco criterios de calidad: cuatro relativosa la medicación dispensada al paciente y uno relativo a laidentificación del mismo. Paralelamente, se diseñó un protocolode trabajo estandarizado y se evaluó el cumplimiento de los criteriossobre todos los cajetines de medicación de los pacientes hospitalizadosen dos unidades clínicas. El cumplimiento de los criteriosse midió antes y después de la implantación del protocolo,durante catorce y siete días consecutivos respectivamente.Resultados: En la primera evaluación el número de incumplimientosfue 0,84/cajetín. Tras la implantación del protocolo, eltotal de incumplimientos tras ajuste por tamaño de muestra seredujo a 0,22/cajetín. El nivel de cumplimiento mejoró para todoslos criterios y las diferencias fueron significativas para los dos criteriosmás incumplidos.Conclusiones: La implantación de un protocolo ha supuestouna mejora significativa en dos de los cinco criterios estudiados enel proceso llenado de carros de medicación. La identificación delpaciente se ha revelado como un aspecto fundamental de intervenciónen la calidad de la dispensación

Objective: To assess the quality of filling medication trolleysprocess for an unit-dose drug distribution system, after the implantationof a protocol.Method: Five criteria were defined: four were related to themedication given to the patient, and one criterion was related tothe patient’s identification. At the same time, it was designed astandardized protocol of filling medication trolleys process and itwas evaluated the degree of compliance with the criteria on all thehospitalized patients’ medication drawers in two clinical units. Thefulfilment of the criteria was measured both before and after theimplantation of the protocol, for fourteen and seven days respectively.Results: In the first evaluation the number of errors was0.84/medication drawer. After the implantation of the protocol,the total number of errors after correction for sample size decreasedat 0.22/medication drawer. The degree of compliance improvedfor all the criteria, and differences were statistically significantfor the criteria with most errors.Conclusions: The implantation of a protocol significantlyimproved two of the five quality criteria studied in the filling medicationtrolleys process. The patient's identification has been revealedas a fundamental aspect of intervention in the dispensationquality

Pharmacokinetics of azithromycin after i.v. and i.m. administration to sheep.

The pharmacokinetics (PK) of azithromycin after i.v. and i.m. injection at a single dosage of 20 mg/kg bodyweight was studied in sheep. Blood samples were collected from the jugular vein until 120 h after dosing for both routes. Plasma concentrations of azithromycin were determined by bioassay. The plasma concentration-time data of azithromycin best fitted a three-compartment model after i.v. administration and a two-compartment model with first-order absorption after i.m. administration. The elimination half-life (t(1/2lambdaz)) was 47.70 +/- 7.49 h after i.v. administration and 61.29 +/- 13.86 h after i.m. administration. Clearance value after i.v. dosing was 0.52 +/- 0.08 L/kg.h. After i.m. administration a peak azithromycin concentration (C(max)) of 1.26 +/- 0.19 mg/L was achieved at 1.24 +/- 0.31 h (t(max)). Area under the curve (AUC) were 38.85 +/- 5.83 mg.h/L and 36.03 +/- 1.52 mg.h/L after i.v. and i.m. administration respectively. Bioavailability obtained after i.m. administration was 94.08 +/- 11.56%. The high tolerability of this i.m. preparation and the favourable PK behaviour such as the long half-life and high bioavailability make azithromycin likely to be effective in sheep.

Pharmacokinetic-pharmacodynamic integration of moxifloxacin in rabbits after intravenous, intramuscular and oral administration.

The pharmacokinetics of moxifloxacin was studied following intravenous (i.v.), intramuscular (i.m.) and oral dose of 5 mg/kg to healthy white New Zealand rabbits (n = 6). Moxifloxacin concentrations were determined by HPLC assay with fluorescence detection. The moxifloxacin plasma concentration vs. time data after i.v. administration could best be described by a two-compartment open model. The disposition of i.m. and orally administered moxifloxacin was best described by a one-compartment model. The plasma moxifloxacin clearance (Cl) for the i.v route was (mean +/- SD) 0.80 +/- 0.02 L/h.kg. The steady-state volume of distribution (Vss) was 1.95 +/- 0.18 L/kg. The terminal half-life (t(1/2lambdaz)) was (mean +/- SD) 1.84 +/- 0.12, 2.09 +/- 0.05 and 2.15 +/- 0.07 h after i.v., i.m. and oral, respectively. Minimal inhibitory concentration (MIC) assays of moxifloxacin against different strains of S. aureus were performed in order to compute pharmacodynamic surrogate markers. From these data, it is concluded that a 5 mg/kg dose moxifloxacin would be effective by i.m. and oral routes in rabbits against bacterial isolates with MIC < or = 0.06 microg/mL and possibly for MIC < or = 0.12 microg/mL, but in the latter case a higher dose would be required.

Pharmacokinetics of azithromycin after intravenous and intramuscular administration to goats.

Azithromycin is the first of a class of antimicrobial agents designated azalides. The aim of the present study was to investigate the disposition pharmacokinetics of azithromycin in goats and determine its bioavailability. A cross-over study was carried out in two phases separated by 30 days. Azithromycin was administered at a single dose of 20 mg/kg body weight by i.v. and i.m. routes. Plasma concentrations of azithromycin were determined by a modified agar diffusion bioassay. After a single i.v. dose plasma concentrations were best fitted to a three-compartment open model. A two-compartment open model with first-order absorption fitted best after i.m. administration. The values of the pharmacokinetic parameters after i.v. administration were: half-life 32.5 h, apparent volume of distribution at the steady-state 34.5 L/kg, clearance 0.85 L/kg. and mean residence time (MRT) 40.1 h. After i.m. administration half-life of 45.2 h, a MRT of 60.3 h, maximum plasma concentration 0.64 mg/L and a bioavalability 92.2% were obtained. The pharmacokinetic parameters of azithromycin after i.m. administration, principally its long half-life and high bioavailability, could provide an alternative to the oral route of administration in goats, although more studies are needed to establish a suitable pharmaceutical formulation, propose optimun dosage regimens, investigate clinical efficacy and study the tolerability of repeated doses.

[Quality improvement of the filling medication trolleys process, for an unit-dose drug distribution system]. / Mejora de la calidad del proceso de llenado de carros de medicación en un sistema de distribución de medicamentos en dosis unitarias.

OBJECTIVE: To assess the quality of filling medication trolleys process for an unit-dose drug distribution system, after the implantation of a protocol. METHOD: Five criteria were defined: four were related to the medication given to the patient, and one criterion was related to the patient's identification. At the same time, it was designed a standardized protocol of filling medication trolleys process and it was evaluated the degree of compliance with the criteria on all the hospitalized patients medication drawers in two clinical units. The fulfilment of the criteria was measured both before and after the implantation of the protocol, for fourteen and seven days respectively. RESULTS: In the first evaluation the number of errors was 0.84/medication drawer. After the implantation of the protocol, the total number of errors after correction for sample size decreased at 0.22/medication drawer. The degree of compliance improved for all the criteria, and differences were statistically significant for the criteria with most errors. CONCLUSIONS: The implantation of a protocol significantly improved two of the five quality criteria studied in the filling medication trolleys process. The patient's identification has been revealed as a fundamental aspect of intervention in the dispensation quality.

Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to sheep.

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination were studied in 6 sheep, after intravenous and intramuscular injection at a single dose rate of 20 mg/kg body weight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open 2-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.32+/-0.06 L/kg and 0.42+/-0.04 L/kg, respectively and the total body clearances were 0.69+/-0.07 and 0.38+/-0.03 L/kg x h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.32+/-0.05 h and 0.75+/-0.27 h, respectively, whereas for sulbactam the half-lives were 0.74+/-0.10 h and 0.89+/-0.16 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (72.76+/-9.65% for ampicillin and 85.50+/-8.35% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.25+/-0.10 h and 0.24+/-0.08 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.01+/-7.36 mg/L of ampicillin and 10.39+/-3.95 mg/L of sulbactam). Both drugs had a similar pharmacokinetic behavior after intramuscular administration in sheep. Since the plasma concentrations of sulbactam where consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a higher than 2:1 ratio.

Some pharmacokinetic parameters of ampicillin/sulbactam combination after intravenous and intramuscular administration to goats.

Some pharmacokinetic parameters of an ampicillin/sulbactam (2:1) combination were studied in six goats, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open two-compartment model. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.34 +/- 0.04 l/kg and 0.45 +/- 0.15 l/kg, respectively, and the total body clearances were 0.72 +/- 0.11 and 0.38 +/- 0.07 l/kg.h. The half-lives of ampicillin after intravenous and intramuscular administration were 0.32 +/- 0.04 h and 0.71 +/- 0.14 h, respectively. For sulbactam the half-lives were 0.79 +/- 0.18 h and 1.13 +/- 0.21 h after administration by the same routes. The bioavailability after intramuscular injection was high and similar for both drugs (98.29% for ampicillin and 101.84% for sulbactam). The mean peak plasma levels of ampicillin (0.43 +/- 0.27 h) and sulbactam (0.34 +/- 0.14 h) were reached at a similar time, and peak concentrations were also similar and non-proportional to the dose of the products administered (11.02 +/- 3.11 mg/l of ampicillin and 9.5 +/- 0.98 mg/l of sulbactam).

Single-dose pharmacokinetics of ampicillin/sulbactam (2:1) combination after intravenous administration to sheep and goats.

The pharmacokinetic behaviour of a combination of ampicillin and sulbactam (2:1) in six sheep and six goats after single intravenous doses of 20 mg kg body weight-1 (13.33 mg kg-1 of ampicillin and 6.67 mg kg-1 of sulbactam) was investigated by using a high-performance liquid chromatographic method for determining plasma concentrations. The objective was to determine whether there are differences between sheep and goats in the disposition kinetics of ampicillin and sulbactam. The plasma concentration-time curves were analysed by compartmental pharmacokinetic and non-compartmental methods. The disposition curves for both drugs were best described by a biexponential equation (two-compartment open model) in both sheep and goats. The mean (SD) elimination half-lives of ampicillin were 0.32 (0.05) h in sheep and 0.32 (0.04) h in goats, and the half-lives of sulbactam were 0.74 (0.10) h and 0.79 (0.18) h in sheep and goats, respectively. The apparent volumes of distribution of ampicillin and sulbactam were similar in the two species. Mean (SD) body clearances of ampicillin were 0.69 (0.07) litre h-1 kg-1 in sheep and 0.72 (0.11) litre h-1 kg-1 in goats, and the body clearances of sulbactam were 0.38 (0.03) and 0.38 (0.07) litre h-1 kg-1 in sheep and goats, respectively. There were no significant differences between any of the pharmacokinetic parameters of ampicillin and sulbactam in the sheep and goats.

Comparative pharmacokinetics of an ampicillin/sulbactam combination administered intramuscularly in lactating sheep and goats.

The pharmacokinetic behaviour of an ampicillin/sulbactam (2:1) combination was studied after intramuscular administration of a single dose (20 mg/kg body weight: 13.33 mg/kg of ampicillin and 6.67 mg/kg of sulbactam) to six sheep and six goats. The objective was to determine whether there were differences between sheep and goats in the disposition profiles of ampicillin and sulbactam. The disposition curves for both drugs were best described by a biexponential equation (one-compartment open model with first order absorption) in both sheep and goats. The maximum plasma concentrations of ampicillin and sulbactam were similar in both sheep (10.61 +/- 6.36 and 9.17 +/- 3.82 mg/L respectively) and goats (11.02 +/- 2.69 and 9.25 +/- 0.85 mg/L respectively), in spite of the fact that the ampicillin dose was twice that of sulbactam. The time of the peak plasma concentration for both drugs was also similar in both sheep and goats. The elimination half-life of ampicillin was 0.81 +/- 0.17 h in sheep and 0.71 +/- 0.12 h in goats, and that of sulbactam was 1.02 +/- 0.36 h in sheep and 1.13 +/- 0.18 h in goats. The rate of drug removal from the body was faster in sheep than in goats and consequently the area under the curve was greater for goats. It was concluded that the similarity in the disposition and elimination of both drugs in sheep and goats indicated that the combination preparation could be administered at the same dosing rate in both species.