Alfred Chin

Utility of a transdermal delivery system for antihypertensive therapy. Part 1

A retrospective evaluation of patient-level Medicaid claims data from two states was undertaken to discern the fiscal utility of transdermally delivered clonidine versus both the oral formulation of clonidine and oral formulations of eight other antihypertensive agents. In the first phase of our two-part study, we compared paid claims data (n = 1,135) from Florida for transdermal and oral clonidine. Multivariate regression analysis was used to evaluate the incremental impact of six variables on health-care expenditures in the first year after patients were given a diagnosis of hypertension. These variables were: age, gender, prior utilization of medical services, regimen complexity, and dosage formulation. Patients prescribed transdermal clonidine experienced a significant (p less than or equal to 0.001) increase in prescription expenditures and significant reductions in the use of physician (p less than or equal to 0.05), laboratory (p less than or equal to 0.10), and hospital (p less than or equal to 0.05) services. Moreover, savings were maximized (p less than or equal to 0.001) where multi-drug regimens incorporated the transdermal delivery system. In the second phase of our study we compared paid claims data (n = 8,894) from South Carolina for transdermal clonidine and for nine oral antihypertensive agents: atenolol, captopril, clonidine, diltiazem, enalapril, metoprolol, prazosin, terazosin, and verapamil-SR. Once again, regression analysis was used, this time to evaluate the incremental impact of five variables on health-care expenditures in the first year post diagnosis: age, gender, prior utilization of medical services, regimen complexity, and Medication Possession Ratio (MPR), an index of compliance. The data from part 2 of our study revealed that patients assigned a b.i.d. oral antihypertensive agent experienced a significant reduction (p less than or equal to 0.05) in MPR and a significant (p less than 0.05) increase in health-care expenditures when compared to patients prescribed the transdermal delivery system and to patients prescribed once-daily oral medications. These data confirm previous findings concerning the impact of complicated dosing regimens on compliance in hypertensive patients. In this two-part paper we report the data from both phases of our study.

Analysis of Cefepime Tissue Penetration Into Human Appendix

Cefepime is a new extended‐spectrum cephalosporin with gram‐positive and gram‐negative coverage including Staphylococcus aureus and Pseudomonas aeruginosa. We evaluated the drugs plasma, peritoneal fluid, and appendix tissue concentrations in patients with a postoperative diagnosis of perforated or gangrenous appendicitis. Patients 18 years of age or older were randomly assigned to receive either cefepime 2 g every 12 hours plus metronidazole 500 mg every 6 hours intravenously, or gentamicin 1.5 mg/kg plus clindamycin 900 mg every 8 hours intravenously. During surgery, appendix tissue, plasma, and peritoneal fluid samples were obtained, and frozen at −70°C for high‐pressure liquid chromatographic analysis. Thirty‐five patients with perforated (26) or gangrenous (9) appendicitis had concentrations acceptable for analysis. The mean time between the administration of cefepime and the time of sampling (referred to as A time) was 5.99 ± 3.75 hours (mean ± SD). The values for plasma (n=34), tissue (n=33), and peritoneal fluid (n=25) concentrations were 16.27 ± 21.87 μg/ml, 4.84 ± 6.15 μg/g, and 14.4 ± 22.84 μg/ml, respectively. The appendix tissue:plasma ratio was 0.66 ± 0.52 and the peritoneal fluid:plasma ratio was 0.66 ± 0.51. Spearman rank correlations indicated statistically significant correlations between plasma concentration (r=‐0.889; p<0.0001), peritoneal fluid concentration (r=‐0.783; p=0.0002), and appendix tissue concentration (r=‐0.704; p=0.0016) versus Δ time. There was a significant correlation between peritoneal fluid and plasma concentration (r=0.853; p<0.0001), and appendix tissue and plasma concentration (r=0.815; p=0.0001). These results indicate that tissue and peritoneal fluid concentrations are approximately 51% and 74%, respectively, of a simultaneous plasma sampling after approximately 5.8 hours.

Tissue concentrations of cefepime in acute cholecystitis patients

Cefepime is a new broad-spectrum cephalosporin with activity against Staphylococcus, Streptococcus, Pseudomonas, and the Enterobacte-riaceae. The purpose of this study was to measure cefepime concentrations in plasma, peritoneal fluid, bile fluid and appendix tissue in patients undergoing elective cholecystectomy. Patients were randomly assigned to receive either cefepime, 2 g intravenously in phosphate buffer (IVPB) q 12 h or gentamicin 1.5 mg/kg IVPB q 8 h plus mezlocillin 4 g IVPB q 6 h. During surgery, gall bladder tissue, plasma, peritoneal fluid, and bile fluid samples were obtained at approximately the same time. Thirty-three patients had data acceptable for analysis. Values are given as mean ± standard deviation. The mean delta time (defined as the time between the administration of cefepime and the time the samples were obtained) was 8.58 ± 3.53 h. The values for plasma, peritoneal fluid, bile fluid, and gall bladder tissue concentrations were 7.63 ± 14.17 μg/ml, 5.66 ± 6.80 μg/ml, 15.51 ± 16.94 μg/ml, and 5.36 ± 6.57 μg/gm, respectively. The peritoneal fluid/plasma ratio was 2.10 ± 2.33, the bile fluid/plasma ratio was 14.44 ± 31.99, and the gall bladder tissue/plasma ratio was 1.34 ± 1.82. There was a significant correlation between peritoneal fluid and plasma concentration (r = 0.91, p < 0.0005), and gall bladder tissue and plasma concentration (r = 0.90, p < 0.0005). There was no correlation between bile fluid and plasma cefepime concentrations. The minimum inhibitory concentration (MIC) data from previous in vitro studies indicate that cefepime concentrations achieved in this patient population would be adequate against typical biliary tract pathogens. This was supported by the fact that there were no clinical failures in any of these patients receiving cefepime. Cefepime appears to be an appropriate choice for prophylactic use in biliary surgery.

Effect of antihypertensive formulation on health service expenditures.

A Major barrier to the management of hypertension is the extent to which patients comply with the treatment regimen. Herein we report the findings of a retrospective analysis designed to discern the relationship between antihypertensive formulation, regimen compliance and the utilization of health care services. Data for this analysis were derived from the state of South Carolinas Medicaid computer archive. The study population consisted of 1 000 randomly selected beneficiaries initially prescribed one of the following antihypertensive regimens as monotheraphy: atenolol (daily); captopril (twice daily); oral clonidine (twice daily); transdermal clonidine (once a week); diltiazem (twice daily); enalapril (twice daily); metoprolol (twice daily); prazosin (twice daily); terazosin (daily); and verapamil-SR (daily). Multivariate regression analysis was used to determine the incremental influence of selected demographic characteristics, utilization of medical services prior to diagnosis for hypertension, initial antihypertensive medication, medication possession ratio for antihypertensive therapy, and the number of maintenance medications for disease state processes other than hypertension on post-period health care expenditure. Results indicate that patients initially prescribed antihypertensive medication requiring daily or weekly administration experience infrequent changes in their therapeutic regimen, far less use of concomitant therapy for blood pressure control, an increased utilization of antihypertensive medication, and a decrease in the use and cost of physician, hospital and laboratory services.A Major barrier to the management of hypertension is the extent to which patients comply with the treatment regimen. Herein we report the findings of a retrospective analysis designed to discern the relationship between antihypertensive formulation, regimen compliance and the utilization of health care services. Data for this analysis were derived from the state of South Carolinas Medicaid computer archive. The study population consisted of 1 000 randomly selected beneficiaries initially prescribed one of the following antihypertensive regimens as monotheraphy: atenolol (daily); captopril (twice daily); oral clonidine (twice daily); transdermal clonidine (once a week); diltiazem (twice daily); enalapril (twice daily); metoprolol (twice daily); prazosin (twice daily); terazosin (daily); and verapamil-SR (daily). Multivariate regression analysis was used to determine the incremental influence of selected demographic characteristics, utilization of medical services prior to diagnosis for hypertension, initial antihypertensive medication, medication possession ratio for antihypertensive therapy, and the number of maintenance medications for disease state processes other than hypertension on post-period health care expenditure. Results indicate that patients initially prescribed antihypertensive medication requiring daily or weekly administration experience infrequent changes in their therapeutic regimen, far less use of concomitant therapy for blood pressure control, an increased utilization of antihypertensive medication, and a decrease in the use and cost of physician, hospital and laboratory services.

Evaluation of two different dosage regimens of clindamycin and the penetration into human appendix

The study objective was to evaluate serum, peritoneal fluid, and appendix tissue concentrations of clindamycin using two differing clindamycin regimens. Patients age 16 years and older who were about to undergo appendectomies were randomly assigned to receive gentamicin 1.5 mg/kg every 8 h admixed with clindamycin 900 mg every 8 h (8-h group) or clindamycin 600 mg every 6 h given separately (6-h group). Doses of each regimen were given preoperatively. Serum, peritoneal fluid, and appendix tissue samples were obtained intraoperatively, and frozen at -70 degrees C for gas chromatographic drug analysis. Twenty-one patients were evaluated, 11 patients in the 8-h group and 10 patients in the 6-h group. Values are reported as means +/- standard deviations. The values in the 8-h group were 12.3 +/- 14.1 micrograms/ml, 8.7 +/- 3.9 micrograms/ml, and 9.8 +/- 10.3 micrograms/g for serum, peritoneal fluid, and appendix tissue, respectively. The values in the 6-h group were 9.7 +/- 5.1 micrograms/ml, 5.8 +/- 5.3 micrograms/ml, and 6.2 +/- 4.9 micrograms/g for serum, peritoneal fluid, and appendix tissue, respectively. The 6-h group received more doses preoperatively (1.8 +/- 0.6) than the 8-h group (1.2 +/- 0.4; p less than 0.05). No differences in penetration of clindamycin into the serum, peritoneal fluid, and appendix tissue for the 8-h group and the 6-h group were noted. The study revealed a similarity in penetration of clindamycin into the serum, peritoneal fluid, and appendix tissue using either clindamycin 900 mg given by intermittent intravenous infusion every 8 h admixed with gentamicin or clindamycin 600 mg given every 6-h separately.

Cost analysis of two clindamycin dosing regimens.

A clinical trial of clindamycin 900 mg q8h admixed with gentamicin 1.5 mg/kg (eight-hourly group) versus clindamycin 600 mg q6h with gentamicin 1.5 mg/kg given separately (six-hourly group) was analyzed for relative cost containment. Acquisition costs were significantly higher for the six-hourly group for intravenous supplies (

Cost analysis of cefmetazole versus cefoxitin in the treatment of penetrating abdominal trauma

181.5 ± 47.8) when compared with the eight-hourly group (

Cefepime: a new fourth-generation cephalosporin

67.6 ± 21.6) (p<0.05). Nursing administration costs were greater for the six-hourly group (

Pharmacokinetic population parameters for aminoglycosides in cholecystitis patients

28.6 ± 7.5) compared with (

Five-Day Stability of Vinorelbine in 5% Dextrose Injection and in 0.9% Sodium Chloride Injection at Room Temperature

10.7 ± 3.4) for the eight-hourly group (p<0.05). Also, significantly higher cost (p<0.05) was noted for pharmacist and technician manufacturing cost for the six-hourly group (