scholarly journals Important pharmacogenomic aspects in the management of HIV/AIDS

2019 ◽  
Vol 61 (1) ◽  
Author(s):  
A. Marais ◽  
E. Osuch ◽  
V. Steenkamp ◽  
L. Ledwaba
Keyword(s):  
South African ◽  
Plasma Levels ◽  
Drug Exposure ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Metabolizing Enzymes ◽  
Highly Active ◽  
Adequate Dosage ◽  
Hiv Aids

In managing HIV/AIDS with highly active antiretroviral agents, the historical therapeutic aim remains to maintain the plasma concentrations at a level above the half maximal inhibitory concentration (IC50) required for 50% inhibition in viral replication. Concentration dependent toxicity is often observed in patients with elevated drug exposure and high peak plasma levels in lieu of accurately calculated drug dosages. Similarly low plasma concentrations are frequently witnessed in individuals receiving adequate dosage regimens. Pharmacogenetic variations in drug metabolizing enzymes may contribute to this phenomenon. Over the last decade, knowledge about the role of pharmacogenetics in the treatment and prediction of ARV plasma levels have increased significantly. However, the extent of these genetic variations remain largely unknown in the South African population, which has sparked a renewed enthusiasm for local pharmacogenetic studies.

EFFECTS OF PINEALECTOMY ON THE SECRETION OF LUTEINIZING HORMONE, TESTOSTERONE AND PROLACTIN IN RAMS EXPOSED TO VARIOUS LIGHTING RÉGIMES

1979 ◽  
Vol 80 (3) ◽  
pp. 397-405 ◽  
Author(s):  
G. K. BARRELL ◽  
K. R. LAPWOOD
Keyword(s):  
Luteinizing Hormone ◽  
Pineal Gland ◽  
Plasma Levels ◽  
Seasonal Changes ◽  
Peak Plasma ◽  
Plasma Concentrations

Two experiments were carried out to study the effects of controlled lighting régimes on plasma levels of LH, testosterone and prolactin in Romney rams. In the second experiment the rams were either pinealectomized or sham-operated so that the role of the pineal gland in mediating seasonal changes in reproduction could be examined. Levels of testosterone and prolactin were considerably influenced by the lighting schedule. Peak plasma concentrations of testosterone were associated with periods during which the daily photoperiod decreased, whereas plasma levels of prolactin showed a pattern of changes approximately in phase with the lighting cycles. Mean plasma concentrations of LH were low in all groups of rams, which made the detection of significant effects of any treatment very unlikely. Pinealectomy reduced the effects of changes in the daily photoperiod on the patterns of secretion of testosterone and prolactin. These findings establish the pineal gland as an organ which influences the endocrine responses of rams to photoperiodic stimuli and it is concluded that the pineal gland is probably important as a mediator of seasonal reproductive changes in these animals.

scholarly journals The essential role of physiotherapists in providing rehabilitation services to people living with HIV in South Africa

2013 ◽  
Vol 69 (1) ◽  
Author(s):  
S. Cobbing ◽  
V. Chetty ◽  
J. Hanass-Hancock ◽  
J. Jelsma ◽  
H. Myezwa ◽  
...  
Keyword(s):  
South Africa ◽  
South African ◽  
Policy Formulation ◽  
People Living With Hiv ◽  
Highly Active ◽  
Hiv Epidemic ◽  
Wide Range ◽  
Living With Hiv ◽  
Education Courses

Despite increased access to highly active anti-retroviral therapy (HAART) in South Africa, there remains a high risk of people living with HIV (PLHIV) developing a wide range of disabilities. Physiotherapists are trained to rehabilitate individuals with the disabilities related to HIV. Not only can South African physiotherapists play a significant role in improving the lives of PLHIV, but by responding proactively to the HIV epidemic they can reinforce the relevance and value of the profession in this country at a time when many newly qualified therapists are unable to secure employment. This paper offers recommendations that may help to fuel this response. These ideas include enhancing HIV curricula at a tertiary level, designing and attending continuing education courses on HIV and researching Southern African rehabilitation interventions for HIV at all levels of practice. furthermore, it is vital that physiotherapists are at the forefront of directing multi-disciplinary responses to the rehabilitation of PLHIV in order to influence stakeholders who are responsible for health policy formulation. it is hoped that this paper stimulates discussion and further ideas amongst physiotherapists and other health professionals in order to improve the quality and access to care available to PLHIV in South Africa.

Plasma and tissue pharmacokinetics of fosfomycin in morbidly obese and non-obese surgical patients: a controlled clinical trial

2019 ◽  
Vol 74 (8) ◽  
pp. 2335-2340 ◽  
Author(s):  
Christoph Dorn ◽  
David Petroff ◽  
Nancy Neumann ◽  
Alexander Kratzer ◽  
Nahed El-Najjar ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Peak Plasma ◽  
Subcutaneous Tissue ◽  
Plasma Concentrations ◽  
Surgical Patients ◽  
Pharmacokinetic Analysis ◽  
Controlled Clinical Trial ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Tissue Pharmacokinetics

Abstract Objectives To assess the pharmacokinetics and tissue penetration of fosfomycin in obese and non-obese surgical patients. Methods Fifteen obese patients undergoing bariatric surgery and 15 non-obese patients undergoing major intra-abdominal surgery received an intravenous single short infusion of 8 g of fosfomycin. Fosfomycin concentrations were determined by LC-MS/MS in plasma and microdialysate from subcutaneous tissue up to 8 h after dosing. The pharmacokinetic analysis was performed in plasma and interstitial fluid (ISF) by non-compartmental methods. Results Thirteen obese patients (BMI 38–50 kg/m2) and 14 non-obese patients (BMI 0–29 kg/m2) were evaluable. The pharmacokinetics of fosfomycin in obese versus non-obese patients were characterized by lower peak plasma concentrations (468 ± 139 versus 594 ± 149 mg/L, P = 0.040) and higher V (24.4 ± 6.4 versus 19.0 ± 3.1 L, P = 0.010). The differences in AUC∞ were not significant (1275 ± 477 versus 1515 ± 352 mg·h/L, P = 0.16). The peak concentrations in subcutaneous tissue were reached rapidly and declined in parallel with the plasma concentrations. The drug exposure in tissue was nearly halved in obese compared with non-obese patients (AUC∞ 1052 ± 394 versus 1929 ± 725 mg·h/L, P = 0.0010). The tissue/plasma ratio (AUCISF/AUCplasma) was 0.86 ± 0.32 versus 1.27 ± 0.34 (P = 0.0047). Conclusions Whereas the pharmacokinetics of fosfomycin in plasma of surgical patients were only marginally different between obese and non-obese patients, the drug exposure in subcutaneous tissue was significantly lower in the obese patients.

Ibuprofen: Plasma Concentrations in Man

1985 ◽  
Vol 13 (1) ◽  
pp. 68-73 ◽  
Author(s):  
G M E Janssen ◽  
J F Venema
Keyword(s):  
Side Effects ◽  
Crossover Study ◽  
Plasma Levels ◽  
Healthy Subjects ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Repeated Dose ◽  
Similar Range ◽  
The Mean ◽  
Peak Value

The plasma levels of Ibuprofen were measured in five healthy subjects who took 600 mg tablets of Ibuprofen twice daily, three times daily and four times daily in a crossover study. Peak plasma levels were obtained 1 hour after the first dose in all but one subject (slow absorber), the mean peak value being 51·3 μg.ml−1 (range 39·4–63·7 μg.ml−1). After the repeated dose regimens of two, three or four times daily of ibuprofen, the peak levels achieved were in a similar range to those seen after the first dose: Twice daily 39·4–66·4 μg.ml−1 Three times daily 43·6–63·3 μg.ml−1 Four times daily 44·1–58·4 μg.ml−1 There was no evidence of accumulation of the drug and no side-effects occurred during the trial.

Intranasal Cocaine: Dose Relationships of Psychological Effects and Plasma Levels

1983 ◽  
Vol 12 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Craig Van Dyke ◽  
James Ungerer ◽  
Peter Jatlow ◽  
Paul Barash ◽  
Robert Byck
Keyword(s):  
Plasma Concentration ◽  
Plasma Levels ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Psychological Effects ◽  
Acute Tolerance ◽  
Lidocaine Hydrochloride ◽  
Intranasal Cocaine ◽  
Cocaine Hydrochloride ◽  
Repeated Doses

We compared the psychological effects of three doses of intranasal cocaine hydrochloride (.2, .75, and 1.5 mg/kg) with cocaine plasma concentrations in four volunteers. Intranasal lidocaine hydrochloride (.2 mg/kg) was used as a topically active placebo. Peak “high” ratings were related to both dose and peak plasma concentrations. At a given plasma concentration, “high” ratings were greater when plasma levels were increasing than when they were decreasing. This indicates that acute tolerance by tachyphylaxis occurred after single doses. The cocaine “high” was a pleasant feeling but was without distinctive sensations. The dramatic effects of intranasal cocaine on the street may be related to larger or repeated doses as well as the setting.

An open-label phase I dose escalation study of KRN951, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and 1 in a 4 week on, 2 week off schedule in patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2034-2034 ◽  
Author(s):  
F. A. Eskens ◽  
A. Planting ◽  
L. Van Doorn ◽  
T. Isoe ◽  
K. Hayashi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Drug Exposure ◽  
Kinase Inhibitor ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Growth Factor Receptor ◽  
Pharmacokinetic Analysis ◽  
Dose Escalation Study ◽  
Once Daily ◽  
Grade 3

2034 Background: KRN951 inhibits VEGF induced phosphorylation of VEGF receptors (VEGFR)2 and 1 (IC50 of 0.16 and 0.21 nM) and phosphorylation of c-Kit and Platelet Derived Growth Factor Receptor (PDGFR), (IC50 of 1.63 and 1.72 nM). Methods: The principal objectives of this study were (1) to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of KRN951 administered once daily (OD) for 28 days followed by 14 days off treatment, (2) to characterize safety and tolerability, (3) to characterize single and multiple dose pharmacokinetics, (4) to explore inhibitory effects on tumor blood flow, and (5) to look for evidence of antitumor activity. Results: 10 male and 5 female patients, median age 57 yrs (28–72) have been enrolled at dose levels of 1 mg (n=6), 2 mg (n=8), and 1.5 mg (n=1). The total number of courses given is 63 (1–15 per patient) At 2 mg DLT consisting of grade 3 asymptomatic proteinuria, grade 3 ataxia and grade 4 intracranial hemorrhage was seen in three patients. In the next-lower dose level of 1 mg one DLT (grade 3 fatigue) was seen. An intermediate dose of 1.5 mg is currently studied. Hypertension occurred in 14/15 patients but could be medically controlled. Pharmacokinetic analysis revealed dose dependent drug exposure and peak plasma concentrations. Plasma levels of sVEGFR2 decreased following exposure to KRN951. Exploratory analysis by means of Dynamic Contrast Enhanced MRI analysis indicated a decrease in tumorperfusion in selected patients. One confirmed partial response lasting more than 80 weeks in a patient with renal cell carcinoma was seen, and stable disease lasting more than 2 courses of treatment was seen in 6 patients. Conclusion: Once daily KRN951 can be administered safely when given for 28 days followed by 14 days off treatment. The recommended phase II dosing is currently being defined. No significant financial relationships to disclose.

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