Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy

Objectives

The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV‐infected pregnant women receiving lopinavir/ritonavir (LPV/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum.

Methods

Women were enrolled in the study who were receiving the LPV/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C_trough) were compared independently [using analysis of variance (anova )] and on a longitudinal basis (using a paired t‐test).

Results

Forty‐six women were enrolled in the study (38 Black African). Forty women initiated LPV/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15–36) weeks and median (range) baseline CD4 count and viral load were 346 (14–836) cells/μL and 8724 (<50–267408) HIV‐1 RNA copies/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild‐type virus (MEC; 1000 ng/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first/second [3525 (2823–4227) ng/mL; n=16] and third [3346 (2813–3880) ng/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693–6579) ng/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851–4463) ng/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy. However, reduced LPV concentrations in the second/third trimesters and potentially compromised adherence highlight the need for TDM‐guided dose adjustment in certain cases.     

Percutaneous brachial artery catheterization

We describe modifications and suggestions for safer percutaneous catheterization of the brachial artery based in part on the anatomy of the axillary-brachial artery and surrounding nerves of the brachial plexus. The brachial artery approach should be nearly as safe as the femoral artery approach for percutaneous catheterization and should not be avoided if the femoral arteries cannot be used.     

Evaluation of the Toxicity and Reversibility Profile of the Aqueous Seed Extract of Hunteria Umbellata (K. Schum.) Hallier F. in Rodents

Hunteria umbellata (K. Schum.) Hallier f. (family: Apocynaceae) is reputed for the folkloric management of labour, pain and swellings, stomach ulcers, diabetes, obesity, and anaemia, with no scientific report of its toxicity and reversibility profile. The present study was, therefore, aimed at investigating the in vivo toxicity and reversibility profile of the aqueous seed extract of Hunteria umbellata (HU). The acute oral and intraperitoneal toxicity studies of HU were determined in Swiss albino mice while its 90-day oral toxicity and toxicity reversibility profile on anthropometric, biochemical, haematological and histopathological parameters were also assessed using standard procedures. Results showed that the LD₅₀ values for the acute oral and intraperitoneal toxicity studies for HU were estimated to be 1000 mg/kg and 459.3 mg/kg, respectively. Visible signs of immediate and delayed toxicities including starry hair coat, respiratory distress, and dyskinesia were observed. For the chronic oral toxicity study, HU administered for 90 days produced significant (p<0.001) reductions in the weight gain pattern and significant (p<0.001) and dose related increases in the relative weights of liver, stomach, spleen, testis, lungs and heart, at the 100 and 500 mg/kg of HU. Chronic HU treatment also produced significant (p<0.05, p<0.001) dose related reductions in the serum levels of fasting blood glucose, bicarbonate, urea and creatinine while causing non-significant (p>0.05) alterations in the serum levels of sodium, potassium, alaninine transaminase, aspartate transaminase, alkaline phosphatase, total and conjugated bilirubin, total protein and albumin. Also, chronic oral treatment with HU produced significant (p<0.05, p<0.01, p<0.001) and dose-related increases in the red cell count, packed cell volume, haemoglobin concentration, platelet count, total leucocyte count and lymphocyte differential while producing significant (p<0.05) reductions in neutrophil and granulocyte differentials. HU also produced histological features of proliferations of the stomach epithelia, lung tissues, splenic white and red pulps, and testicular spermatogenic series. Following 14 days of oral toxicity reversibility test, there was no significant (p>0.05) reversal in the serum levels of the biochemical and haematological parameters investigated, including the HU-induced histological lesions.Overall, results of this study showed that HU has a relatively low oral toxicity profile but its prolonged use, particularly, at high doses should be with great caution.Key words: Hunteria umbellata, Toxicity and reversibility profile, Haematology, Liver and Renal function tests, Histopathology, Rodents