Levels of contaminant zinc in solutions routinely used in rehydration and/or parenteral feeding

With the objective to evaluate the zinc needs of children submitted to rehydration and/or parenteral nutrition, the content of contaminating zinc was determined in intravenous solutions utilized at University Hospital of Ribeir?o Preto, SP, Brazil. Zinc was measured in 40 bottles containing deionized water and submitted to the routine treatment for industrialization of serum for parenteral use, according to the standards of the University Hospital of Ribeir?o Preto, Industrial Pharmacy. The effect of the sealing material employed (polished red stopper and unpolished black stopper) was observed, as well as time of contact between the solutions and rubber stoppers and latex slides, and the method of bottle conditioning (vertical or horizontal position) which permits contact of the solutions with the rubber stoppers. The gluco-saline solutions prepared in our Hospital and stored in glass bottles with unpolished black rubber stoppers and latex slide showed substantial zinc levels (1,220 to 4,860 micrograms/ml, n = 30). The same solutions kept in glass vials or plastic bottles were zinc free. The highest zinc levels were observed in the amino acid solutions placed in sealed bottles with unpolished black rubber stoppers (11,690 to 24,310 micrograms/ml, n = 20). It is important to be aware of these contaminating zinc levels to provide proper treatment involving this micronutrient.     

Past, present and future of A(2A) adenosine receptor antagonists in the therapy of Parkinson's disease

Several selective antagonists for adenosine A_2A receptors (A_2AR) are currently under evaluation in clinical trials (phases I to III) to treat Parkinson's disease, and they will probably soon reach the market. The usefulness of these antagonists has been deduced from studies demonstrating functional interactions between dopamine D₂ and adenosine A_2A receptors in the basal ganglia. At present it is believed that A_2AR antagonists can be used in combination with the dopamine precursor L-DOPA to minimize the motor symptoms of Parkinson's patients. However, a considerable body of data indicates that in addition to ameliorating motor symptoms, adenosine A_2AR antagonists may also prevent neurodegeneration. Despite these promising indications, one further issue must be considered in order to develop fully optimized antiparkinsonian drug therapy, namely the existence of (hetero)dimers/oligomers of G protein-coupled receptors, a topic that is currently the focus of intense debate within the scientific community. Dopamine D₂ receptors (D₂Rs) expressed in the striatum are known to form heteromers with A_2A adenosine receptors. Thus, the development of heteromer-specific A_2A receptor antagonists represents a promising strategy for the identification of more selective and safer drugs.     

Pharmacokinetics of Fosamprenavir plus Ritonavir in Human Immunodeficiency Virus Type 1-Infected Adult Subjects with Hepatic Impairment

The effect of hepatic impairment on fosamprenavir/ritonavir pharmacokinetics was investigated. Sixty human immunodeficiency virus type 1-infected subjects, including 13, 20, and 10 subjects with mild, moderate, and severe hepatic impairment, respectively, and a comparator group of 17 subjects with normal hepatic function, were enrolled. Subjects with normal hepatic function received fosamprenavir at 700 mg plus ritonavir at 100 mg twice daily, whereas subjects with hepatic impairment received adjusted doses in anticipation of increased exposures. For subjects with mild hepatic impairment, the studied regimen of fosamprenavir 700 mg twice daily plus ritonavir 100 mg once daily delivered 17% higher values for the maximum plasma amprenavir concentration at the steady state (C_max), 22% higher values for the area under the plasma concentration versus time curve over the dosing interval at the steady state [AUC_(0-τ)], similar values for the concentration at the end of the dosing interval (C_τ), and 114% higher unbound C_τ values. For subjects with moderate hepatic impairment, the studied dosage regimen of fosamprenavir at 300 mg twice daily plus ritonavir at 100 mg once daily delivered 27% lower plasma amprenavir C_max values, 27% lower AUC_(0-24) values, 57% lower C_τ values, and 21% higher unbound amprenavir C_τ values. For subjects with severe hepatic impairment, the studied dosage regimen of fosamprenavir at 300 mg twice daily plus ritonavir at 100 mg once daily delivered 19% lower plasma amprenavir C_max values, 23% lower AUC_(0-24) values, 38% lower C_τ values, and similar unbound amprenavir C_τ values. With a reduced ritonavir dosing frequency of 100 mg once daily, the plasma ritonavir AUC_(0-24) values were 39% lower, similar, and 40% higher for subjects with mild, moderate, and severe hepatic impairment, respectively. The results of the study support the use of reduced fosamprenavir/ritonavir doses or dosing frequencies in the treatment of patients with hepatic impairment. No significant safety issues were identified; however, plasma amprenavir and ritonavir exposures were more variable in subjects with hepatic impairment, and those patients should be closely monitored for safety and virologic response.Among the estimated 40 million persons infected with human immunodeficiency virus (HIV) worldwide, an estimated 2 to 4 million are chronically infected with hepatitis B virus (HBV) and an estimated 4 to 5 million are chronically infected with hepatitis C virus (HCV) (1). The prevalence of HBV and HCV coinfection in HIV-infected subjects is correlated with intravenous drug use as an HIV risk factor; the prevalence is above 40% in some southern European countries (2, 5, 7). Those with hepatitis infection often have some degree of liver impairment. For those with chronic HCV infection alone, the estimated rate of progression to cirrhosis is 2 to 20% over 20 years (1).Dosing recommendations for the hepatically impaired are available for several protease inhibitors, although most exclude those with severe impairment and/or include safety precautions. Until recently, unboosted amprenavir was the only protease inhibitor indicated for use in the treatment of HIV-infected patients with severe hepatic impairment; indeed, all antiretroviral agents other than selected nucleosides are contraindicated for this difficult-to-treat population. Thus, more options are clearly needed.Fosamprenavir is the prodrug of the HIV type 1 (HIV-1) protease inhibitor amprenavir and is often used in combination with low-dosage ritonavir to increase plasma amprenavir concentrations by inhibiting amprenavir CYP3A4-mediated metabolism. We studied fosamprenavir/ritonavir combinations administered to HIV-infected subjects with mild, moderate, and severe hepatic impairment as well as to control subjects with normal hepatic function for 2 weeks. Because amprenavir is highly bound to plasma proteins (including albumin and α₁-acid glycoprotein [AAG]) that are synthesized in the liver, plasma unbound amprenavir concentrations and percent unbound were evaluated in the present study. The primary goals of this study were to evaluate the impact of hepatic impairment on amprenavir and ritonavir pharmacokinetics (PK) and to determine dosing recommendations for this patient population.