Pharmacokinetics of Hydroxyprogesterone Caproate and its Primary Metabolites during Pregnancy.

Objective To measure pharmacokinetics of hydroxyprogesterone caproate (OHPC) and its major metabolites throughout pregnancy. Study Design Thirty women were prescribed OHPC for recurrent preterm birth prevention. Three cohorts of subjects had blood drawn for 7 consecutive days at one of three times: cohort 1 ( n = 6) after the first dose (weeks 16-20), cohort 2 ( n = 8) between weeks 24 and 28, and cohort 3 ( n = 16) between weeks 32 and 36. We measured serum trough levels after week 1 in cohort 1 or after two consecutive weekly doses in cohorts 2 and 3. In 10 subjects, we estimated OHPC terminal half-life at 28 days after their last dose. Results In cohorts 1, 2, and 3, the areas under curve (ng × h/mL) for OHPC were 571.4 ± 195.2, 1,269.6 ± 285.0, and 1,268.0 ± 511.6, respectively. Maximum OHPC levels (ng/mL) were 5.0 ± 1.5, 12.5 ± 3.9, and 12.3 ± 4.9, respectively. The areas under the curve for mono-hydroxylated metabolites were 208.5 ± 92.4, 157.1 ± 64.6, and 211.2 ± 113.1, and maximum concentrations were 1.9 ± 0.7, 1.5 ± 0.7, and 1.8 ± 1.0, respectively. Di-hydroxylated metabolite levels were significantly lower than mono-hydroxylated metabolites. Estimated terminal half-life of OHPC was 16.3 ± 3.6 days and 19.7 ± 6.2 days for the mono-hydroxylated metabolites. Conclusion After the first injection, OHPC maximum serum level was approximately half steady-state level. Measurable metabolites of unknown activity were detected.

Pulmonary embolism after major abdominal surgery in gynecologic oncology.

OBJECTIVE: To estimate the incidence and prognostic significance of postoperative pulmonary embolism after gynecologic oncology surgery. METHODS: All patients who underwent gynecologic oncology surgery from June 2001 to June 2003 and received venous thromboembolism prophylaxis with only intermittent pneumatic compression and early ambulation were identified from our database. Patients were grouped by procedure (major/minor abdominal or nonabdominal surgery), diagnosis (malignant/nonmalignant), and cancer subtype. Groups were compared by chi2 analysis and logistic regression. Survival was studied with the Kaplan-Meier method and Mantel-Byar test. RESULTS: A total of 1,373 surgical patients were identified over the 2-year period, including 839 major abdominal surgery cases and 534 minor abdominal surgery or nonabdominal surgery cases. Of the 839 patients, 507 had a diagnosis of cancer, and 332 were benign. The incidence of pulmonary embolism among cancer patients undergoing major abdominal surgery was 4.1% (21/507) compared with 0.3% (1/332) among patients undergoing major abdominal surgery with benign findings (P < .001, odds ratio [OR] 13.8, 95% confidence interval [CI] 1.9-102.1). The incidence of pulmonary embolism among patients undergoing minor/nonabdominal surgery was 0.4% (2/536). Cancer diagnosis and age more than 60 years were identified as risk factors for pulmonary embolism (P = .009, OR 0.31, 95% CI 0.13-0.74). One-year survival for patients with and those without pulmonary embolism were 48.0% +/- 12% and 77.0% +/- 2%, respectively. CONCLUSION: Patients with cancer undergoing major abdominal surgery and using pneumatic compression for thromboembolic prophylaxis had a 14-fold greater odds of developing a pulmonary embolism compared with patients with benign disease. Randomized studies are needed to determine whether additional prophylactic measures may benefit this high-risk group of patients. LEVEL OF EVIDENCE: II-3.

Diagnosing pulmonary embolism: experience with spiral CT pulmonary angiography in gynecologic oncology.

OBJECTIVES: To review our experience with the diagnosis and prognosis of pulmonary embolism (PE) in gynecologic oncology patients. METHODS: Spiral CT pulmonary angiography (CTPA) studies on gynecologic oncology patients were collected from our radiology database from 6/2001 to 6/2003. Patient charts were retrospectively reviewed. Data were abstracted relative to presenting symptoms, demographics and laboratory and diagnostic evaluations. Patient data were compared using chi-square contingency tables and logistic regression analysis. Survival was studied using the Kaplan-Meier method and the log rank test. The effect of PE on survival was adjusted using a proportional hazards regression model. RESULTS: One-hundred and eleven CTPA studies were performed over 2 years and 25 patients were diagnosed with PE. Both PE (n = 25) and non-PE (n = 86) groups were similar for age, race, BMI and cancer diagnosis. Tachycardia (P = 0.02, OR = 3.03 [95% CI 1.16-7.94]) and leukocytosis (P = 0.04, OR = 2.93[95% CI 1.05-8.18]) were more frequent among PE patients and confirmed as independently prognostic of PE. All other clinical and laboratory findings were similar between patients with and without PE. Overall survival for patients with and without PE was 63% versus 94%, respectively, at 2 years (P = 0.02). CONCLUSION: In a gynecologic oncology patient with high clinical suspicion for PE, our clinical pre-test probability was 23.0%. Two-year mortality rates were 6-fold higher for patients diagnosed with PE. The significant overlap in clinical presentations, multiple risk factors and higher mortality rates encourage the aggressive diagnosis and treatment of PE among this population. Further work is needed to reduce the incidence and mortality rate of PE.