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1.  Semiphysiological versus Empirical Modelling of the Population Pharmacokinetics of Free and Total Cefazolin during Pregnancy 
BioMed Research International  2014;2014:897216.
This work describes a first population pharmacokinetic (PK) model for free and total cefazolin during pregnancy, which can be used for dose regimen optimization. Secondly, analysis of PK studies in pregnant patients is challenging due to study design limitations. We therefore developed a semiphysiological modeling approach, which leveraged gestation-induced changes in creatinine clearance (CrCL) into a population PK model. This model was then compared to the conventional empirical covariate model. First, a base two-compartmental PK model with a linear protein binding was developed. The empirical covariate model for gestational changes consisted of a linear relationship between CL and gestational age. The semiphysiological model was based on the base population PK model and a separately developed mixed-effect model for gestation-induced change in CrCL. Estimates for baseline clearance (CL) were 0.119 L/min (RSE 58%) and 0.142 L/min (RSE 44%) for the empirical and semiphysiological models, respectively. Both models described the available PK data comparably well. However, as the semiphysiological model was based on prior knowledge of gestation-induced changes in renal function, this model may have improved predictive performance. This work demonstrates how a hybrid semiphysiological population PK approach may be of relevance in order to derive more informative inferences.
PMCID: PMC3930089  PMID: 24672799
2.  Cervical cancer in pregnant women: treat, wait or interrupt? Assessment of current clinical guidelines, innovations and controversies 
Cervical cancer during pregnancy is relatively uncommon. However, the incidence is expected to increase as more women delay childbearing. When preservation of the pregnancy is desired, optimal treatment is a major challenge to all. Whereas delay of treatment is an option for pre-invasive disease, and also small invasive carcinomas without lymph node involvement, management of tumours >2 cm remains experimental. Type of treatment needs to be individualized and depends mainly on gestational age, disease stage, and histology. Extensive counselling regarding the maternal and foetal risks is required. In this current review, we aim to summarize available data and treatment guidelines concerning cervical cancer in pregnancy. Controversies and research priorities are also identified.
PMCID: PMC3707341  PMID: 23858330
cervical cancer; chemotherapy; neonatal; pregnancy
3.  Physiologic variations of serum tumor markers in gynecological malignancies during pregnancy: a systematic review 
BMC Medicine  2012;10:86.
Recent insights provide support for the treatment of cancer during pregnancy, a coincidence that poses both mother and fetus at risk. Our aim was to critically review studies on the physiologic variations during pregnancy, the most common tumor markers used in diagnosis and follow-up of gynecological cancers.
We conducted a systematic review of six tumor markers during normal pregnancy: carbohydrate antigen (CA) 15-3 (breast cancer); squamous cell carcinoma antigen (cervical cancer); and CA 125, anti-Müllerian hormone, inhibin B and lactate dehydrogenase (ovarian cancer).
For CA 15-3, 3.3% to 20.0% of all measurements were above the cut-off (maximum 56 U/mL in the third trimester). Squamous cell carcinoma antigen values were above cut-off in 3.1% and 10.5% of the measurements (maximum 4.3 µg/L in the third trimester). Up to 35% of CA 125 levels were above cut-off: levels were highest in the first trimester, with a maximum value up to 550 U/mL. Inhibin B, anti-Müllerian hormone and lactate dehydrogenase levels were not elevated in maternal serum during normal pregnancy.
During normal pregnancy, tumor markers including CA 15.3, squamous cell carcinoma antigen and CA 125 can be elevated; inhibin B, anti-Müllerian hormone and lactate dehydrogenase levels remain below normal cut-off values. Knowledge of physiological variations during pregnancy can be clinically important when managing gynecological cancers in pregnant patients.
PMCID: PMC3425318  PMID: 22873292
anti-Müllerian hormone; CA 125; CA 15-3; cancer; human epididymis secretory protein 4 (HE4); inhibin B; lactate dehydrogenase; pregnancy; squamous-cell carcinoma antigen tumor markers
4.  The Impact of Caesarean Delivery on Paracetamol and Ketorolac Pharmacokinetics: A Paired Analysis 
Pharmacokinetics is a first, but essential step to improve population-tailored postoperative analgesia, also after Caesarean delivery. We therefore aimed to quantify the impact of caesarean delivery on the pharmacokinetics of intravenous (iv) paracetamol (2 g, single dose) and iv ketorolac tromethamine (30 mg, single dose) in 2 cohorts eachof 8 women at caesarean delivery and to compare these findings with postpartum to quantify intrapatient changes. We documented a higher median paracetamol clearance at delivery when compared to 10–15 weeks postpartum (11.7 to 6.4 L/h·m2, P < 0.01), even after correction for weight-related changes. Similar conclusions were drawn for ketorolac: median clearance was higher at delivery with a subsequent decrease (2.03 to 1.43 L/h·m2, P < 0.05) in postpartum (17–23 weeks). These differences likely reflect pregnancy- and caesarean-delivery-related changes in drug disposition. Moreover, postpartum paracetamol clearance was significantly lower when compared to estimates published in healthy young volunteers (6.4  versus  9.6 L/h·m2), while this was not the case for ketorolac (1.43  versus  1.48 L/h·m2). This suggests that postpartum is another specific status in young women that merits focused, compound-specific pharmacokinetic evaluation.
PMCID: PMC3363964  PMID: 22675252
5.  High-grade endometrial stromal sarcoma presenting in a 28-year-old woman during pregnancy: a case report 
To the best of our knowledge, soft tissue sarcomas have not prevously been reported as a complication during pregnancy.
Case presentation
A 28-year-old Caucasian woman was diagnosed with a transperitoneal sarcoma during pregnancy. Morphological, immunohistochemical, chromosomal and mutational analyses pointed towards a high-grade endometrial stromal sarcoma. Although surgery and chemotherapy are possible during pregnancy, we were unable to perform these in this case.
The potential to treat gynecological cancer during pregnancy should always be assessed individually.
PMCID: PMC2925352  PMID: 20684773

Results 1-5 (5)