Interaction of endothelin—1 and prostacyclin during pathological process in patients with ischemic cerebral infarction

Objective :To investigate the interaction and clinical significance of changes in plasma endothelin-1(ET-1) and prostacyclin (PGI2) concentrations in patients with ischemic cerebral infarction.Methods:Plasma ET-1 and 6-keto-PGF1α(resistant metabolite of PGI2) concentrations were measured in 37 pativents(Study group)with ischemic cerebral infarction and 34 healthy volunteers(control group) by radioimmunoassay,Results :Plasma ET-1 concentrations in patients of study group were markedly higher than that of control group(P&;lt;0.01) dioimmunoassay,Results:plasma ET-1 concentrations in patients of study group were markedly higher than that of control group(P&;lt;0.01) and 6-keto-PGF1α concentrations in patients of study group were significantly lower than that of control subjects(P&;lt;0.01),Plasma ET-1 concentrations in control subjects were positively correlated with 6-keto-PGF1α concentrations and no correlation in the study group.COnclusion Both ET-1 and PGI2 are participated in patho-physiologic process of ischemic cerebral infarction.ET-1 is a virulence factor and may play a deleterious role in ischemic cerebral infarction,PGI2 is a conservancy factor and endogenetic antagonist of ET-1,It may provide useful therapy parameter to find out ectogenesis PGI2 or analog for treating the patients with ischemic cerebral infarction with reason.     

HCV核心抗原动态监测抗HCV疗效的临床研究(英文)

Objective To evaluate the performance of Hepatitis C virus (HCV) core antigen and HCV RNA PCR in the determining of the efficacy of HCV antiviral therapy in patients infected with HCV.Methods HCV core antigen and HCV RNA were measured in sera of 35 chronic HCV infected Chinese patients.Concentrations of HCV core antigen and HCV RNA were analyzed at 5 time points before,during and at the end of antiviral therapy.Results This study showed that the HCV core antigen and HCV RNA concentrations in 35 HCV patients were significantly correlated.Decrease of HCV core antigen and HCV RNA concentrations at the 4th,12th,24th and 48th week were observed during the antiviral therapy.However,HCV core antigen levels at week 12 and 24 of therapy were significantly lower than those at week 4 (P<0.05).In contrast,no further decrease was observed in HCV RNA concentrations at weeks 12 and 24 (P>0.05).HCV core antigen testing may be advantageous in some cases,in particular,the low levels of HCV core antigen at week 4 may be predictive of satisfactory outcome of treatment.Conclusions HCV core antigen represents a stable and sensitive marker of viral replication and could be used to monitor the clinical efficacy of HCV antiviral therapy.     

急性高容量血液稀释对全髋关节置换术患者血浆杀菌/通透性增加蛋白表达的影响

Objective To study the effect of acute hypervolemic hemodilution on expression of plasma bac-tericidaL/permeability-increasing protein (BPI) in patients undergoing total hip replacement. Methods Twenty ASA Ⅰ-Ⅱ patients undergoing elective total hip replacement were randomly divided into two groups (n=10 for thesia. The blood loss,blood transfusion and the time of operation were recorded. Venous blood samples were taken before anesthesia (T0) ,at the begining of operation (T1) ,30 min after operation (T2) ,and at the end of operation (T3) for determination of plasma bactericidal/permeability-increasing protein. Results The blood loss and the blood transfusion in HES group were significantly lower than that of LR group[blood loss: (560±90)ml vs (810±110) ml and blood transfusion: (200±100) ml vs (600±200) ml,t=5.562 and 5.657,P<0.001]. The plasma BPI concentrations in HES group were significantly increased at T2～T3 as compared to baseline value at T0 [(8.9±1.6)μg/L,(13.4±1.2)μg/L and (4.9±1.2)μg/L,P<0.05]. The plasma BPI concentrations in LR group were significantly increased at T2～T3 as compared to baseline value at T0 [(7.3±1.2)μg/L,(9.9±0.8) μg/L and (5.0±1.1)μg/L,P<0.05],but were lower than those in HES group (t=2.530 and 7.674,P=0.021 and 0.001 ). Conclusion Acute hypervolemic hemodilution with 200/0.5 hydroxyethyl starch can reduce blood transfusion during total hip replacement operation and also can increase the BPI level which would beneficial for the immunological function.     

急性高容量血液稀释对全髋关节置换术患者血浆杀菌/通透性增加蛋白表达的影响

Objective To study the effect of acute hypervolemic hemodilution on expression of plasma bac-tericidaL/permeability-increasing protein (BPI) in patients undergoing total hip replacement. Methods Twenty ASA Ⅰ-Ⅱ patients undergoing elective total hip replacement were randomly divided into two groups (n=10 for thesia. The blood loss,blood transfusion and the time of operation were recorded. Venous blood samples were taken before anesthesia (T0) ,at the begining of operation (T1) ,30 min after operation (T2) ,and at the end of operation (T3) for determination of plasma bactericidal/permeability-increasing protein. Results The blood loss and the blood transfusion in HES group were significantly lower than that of LR group[blood loss: (560±90)ml vs (810±110) ml and blood transfusion: (200±100) ml vs (600±200) ml,t=5.562 and 5.657,P<0.001]. The plasma BPI concentrations in HES group were significantly increased at T2～T3 as compared to baseline value at T0 [(8.9±1.6)μg/L,(13.4±1.2)μg/L and (4.9±1.2)μg/L,P<0.05]. The plasma BPI concentrations in LR group were significantly increased at T2～T3 as compared to baseline value at T0 [(7.3±1.2)μg/L,(9.9±0.8) μg/L and (5.0±1.1)μg/L,P<0.05],but were lower than those in HES group (t=2.530 and 7.674,P=0.021 and 0.001 ). Conclusion Acute hypervolemic hemodilution with 200/0.5 hydroxyethyl starch can reduce blood transfusion during total hip replacement operation and also can increase the BPI level which would beneficial for the immunological function.     

急性高容量血液稀释对全髋关节置换术患者血浆杀菌/通透性增加蛋白表达的影响

Objective To study the effect of acute hypervolemic hemodilution on expression of plasma bac-tericidaL/permeability-increasing protein (BPI) in patients undergoing total hip replacement. Methods Twenty ASA Ⅰ-Ⅱ patients undergoing elective total hip replacement were randomly divided into two groups (n=10 for thesia. The blood loss,blood transfusion and the time of operation were recorded. Venous blood samples were taken before anesthesia (T0) ,at the begining of operation (T1) ,30 min after operation (T2) ,and at the end of operation (T3) for determination of plasma bactericidal/permeability-increasing protein. Results The blood loss and the blood transfusion in HES group were significantly lower than that of LR group[blood loss: (560±90)ml vs (810±110) ml and blood transfusion: (200±100) ml vs (600±200) ml,t=5.562 and 5.657,P<0.001]. The plasma BPI concentrations in HES group were significantly increased at T2～T3 as compared to baseline value at T0 [(8.9±1.6)μg/L,(13.4±1.2)μg/L and (4.9±1.2)μg/L,P<0.05]. The plasma BPI concentrations in LR group were significantly increased at T2～T3 as compared to baseline value at T0 [(7.3±1.2)μg/L,(9.9±0.8) μg/L and (5.0±1.1)μg/L,P<0.05],but were lower than those in HES group (t=2.530 and 7.674,P=0.021 and 0.001 ). Conclusion Acute hypervolemic hemodilution with 200/0.5 hydroxyethyl starch can reduce blood transfusion during total hip replacement operation and also can increase the BPI level which would beneficial for the immunological function.     

急性高容量血液稀释对全髋关节置换术患者血浆杀菌/通透性增加蛋白表达的影响

Objective To study the effect of acute hypervolemic hemodilution on expression of plasma bac-tericidaL/permeability-increasing protein (BPI) in patients undergoing total hip replacement. Methods Twenty ASA Ⅰ-Ⅱ patients undergoing elective total hip replacement were randomly divided into two groups (n=10 for thesia. The blood loss,blood transfusion and the time of operation were recorded. Venous blood samples were taken before anesthesia (T0) ,at the begining of operation (T1) ,30 min after operation (T2) ,and at the end of operation (T3) for determination of plasma bactericidal/permeability-increasing protein. Results The blood loss and the blood transfusion in HES group were significantly lower than that of LR group[blood loss: (560±90)ml vs (810±110) ml and blood transfusion: (200±100) ml vs (600±200) ml,t=5.562 and 5.657,P<0.001]. The plasma BPI concentrations in HES group were significantly increased at T2～T3 as compared to baseline value at T0 [(8.9±1.6)μg/L,(13.4±1.2)μg/L and (4.9±1.2)μg/L,P<0.05]. The plasma BPI concentrations in LR group were significantly increased at T2～T3 as compared to baseline value at T0 [(7.3±1.2)μg/L,(9.9±0.8) μg/L and (5.0±1.1)μg/L,P<0.05],but were lower than those in HES group (t=2.530 and 7.674,P=0.021 and 0.001 ). Conclusion Acute hypervolemic hemodilution with 200/0.5 hydroxyethyl starch can reduce blood transfusion during total hip replacement operation and also can increase the BPI level which would beneficial for the immunological function.     

急性高容量血液稀释对全髋关节置换术患者血浆杀菌/通透性增加蛋白表达的影响

Objective To study the effect of acute hypervolemic hemodilution on expression of plasma bac-tericidaL/permeability-increasing protein (BPI) in patients undergoing total hip replacement. Methods Twenty ASA Ⅰ-Ⅱ patients undergoing elective total hip replacement were randomly divided into two groups (n=10 for thesia. The blood loss,blood transfusion and the time of operation were recorded. Venous blood samples were taken before anesthesia (T0) ,at the begining of operation (T1) ,30 min after operation (T2) ,and at the end of operation (T3) for determination of plasma bactericidal/permeability-increasing protein. Results The blood loss and the blood transfusion in HES group were significantly lower than that of LR group[blood loss: (560±90)ml vs (810±110) ml and blood transfusion: (200±100) ml vs (600±200) ml,t=5.562 and 5.657,P<0.001]. The plasma BPI concentrations in HES group were significantly increased at T2～T3 as compared to baseline value at T0 [(8.9±1.6)μg/L,(13.4±1.2)μg/L and (4.9±1.2)μg/L,P<0.05]. The plasma BPI concentrations in LR group were significantly increased at T2～T3 as compared to baseline value at T0 [(7.3±1.2)μg/L,(9.9±0.8) μg/L and (5.0±1.1)μg/L,P<0.05],but were lower than those in HES group (t=2.530 and 7.674,P=0.021 and 0.001 ). Conclusion Acute hypervolemic hemodilution with 200/0.5 hydroxyethyl starch can reduce blood transfusion during total hip replacement operation and also can increase the BPI level which would beneficial for the immunological function.     

急性高容量血液稀释对全髋关节置换术患者血浆杀菌/通透性增加蛋白表达的影响

Objective To study the effect of acute hypervolemic hemodilution on expression of plasma bac-tericidaL/permeability-increasing protein (BPI) in patients undergoing total hip replacement. Methods Twenty ASA Ⅰ-Ⅱ patients undergoing elective total hip replacement were randomly divided into two groups (n=10 for thesia. The blood loss,blood transfusion and the time of operation were recorded. Venous blood samples were taken before anesthesia (T0) ,at the begining of operation (T1) ,30 min after operation (T2) ,and at the end of operation (T3) for determination of plasma bactericidal/permeability-increasing protein. Results The blood loss and the blood transfusion in HES group were significantly lower than that of LR group[blood loss: (560±90)ml vs (810±110) ml and blood transfusion: (200±100) ml vs (600±200) ml,t=5.562 and 5.657,P<0.001]. The plasma BPI concentrations in HES group were significantly increased at T2～T3 as compared to baseline value at T0 [(8.9±1.6)μg/L,(13.4±1.2)μg/L and (4.9±1.2)μg/L,P<0.05]. The plasma BPI concentrations in LR group were significantly increased at T2～T3 as compared to baseline value at T0 [(7.3±1.2)μg/L,(9.9±0.8) μg/L and (5.0±1.1)μg/L,P<0.05],but were lower than those in HES group (t=2.530 and 7.674,P=0.021 and 0.001 ). Conclusion Acute hypervolemic hemodilution with 200/0.5 hydroxyethyl starch can reduce blood transfusion during total hip replacement operation and also can increase the BPI level which would beneficial for the immunological function.     

急性高容量血液稀释对全髋关节置换术患者血浆杀菌/通透性增加蛋白表达的影响

Objective To study the effect of acute hypervolemic hemodilution on expression of plasma bac-tericidaL/permeability-increasing protein (BPI) in patients undergoing total hip replacement. Methods Twenty ASA Ⅰ-Ⅱ patients undergoing elective total hip replacement were randomly divided into two groups (n=10 for thesia. The blood loss,blood transfusion and the time of operation were recorded. Venous blood samples were taken before anesthesia (T0) ,at the begining of operation (T1) ,30 min after operation (T2) ,and at the end of operation (T3) for determination of plasma bactericidal/permeability-increasing protein. Results The blood loss and the blood transfusion in HES group were significantly lower than that of LR group[blood loss: (560±90)ml vs (810±110) ml and blood transfusion: (200±100) ml vs (600±200) ml,t=5.562 and 5.657,P<0.001]. The plasma BPI concentrations in HES group were significantly increased at T2～T3 as compared to baseline value at T0 [(8.9±1.6)μg/L,(13.4±1.2)μg/L and (4.9±1.2)μg/L,P<0.05]. The plasma BPI concentrations in LR group were significantly increased at T2～T3 as compared to baseline value at T0 [(7.3±1.2)μg/L,(9.9±0.8) μg/L and (5.0±1.1)μg/L,P<0.05],but were lower than those in HES group (t=2.530 and 7.674,P=0.021 and 0.001 ). Conclusion Acute hypervolemic hemodilution with 200/0.5 hydroxyethyl starch can reduce blood transfusion during total hip replacement operation and also can increase the BPI level which would beneficial for the immunological function.     

急性高容量血液稀释对全髋关节置换术患者血浆杀菌/通透性增加蛋白表达的影响

Objective To study the effect of acute hypervolemic hemodilution on expression of plasma bac-tericidaL/permeability-increasing protein (BPI) in patients undergoing total hip replacement. Methods Twenty ASA Ⅰ-Ⅱ patients undergoing elective total hip replacement were randomly divided into two groups (n=10 for thesia. The blood loss,blood transfusion and the time of operation were recorded. Venous blood samples were taken before anesthesia (T0) ,at the begining of operation (T1) ,30 min after operation (T2) ,and at the end of operation (T3) for determination of plasma bactericidal/permeability-increasing protein. Results The blood loss and the blood transfusion in HES group were significantly lower than that of LR group[blood loss: (560±90)ml vs (810±110) ml and blood transfusion: (200±100) ml vs (600±200) ml,t=5.562 and 5.657,P<0.001]. The plasma BPI concentrations in HES group were significantly increased at T2～T3 as compared to baseline value at T0 [(8.9±1.6)μg/L,(13.4±1.2)μg/L and (4.9±1.2)μg/L,P<0.05]. The plasma BPI concentrations in LR group were significantly increased at T2～T3 as compared to baseline value at T0 [(7.3±1.2)μg/L,(9.9±0.8) μg/L and (5.0±1.1)μg/L,P<0.05],but were lower than those in HES group (t=2.530 and 7.674,P=0.021 and 0.001 ). Conclusion Acute hypervolemic hemodilution with 200/0.5 hydroxyethyl starch can reduce blood transfusion during total hip replacement operation and also can increase the BPI level which would beneficial for the immunological function.     

A combination of poor adherence and a low baseline susceptibility score is highly predictive for HAART failure

The relationship between adherence, virological response to highly active antiretroviral therapy (HAART) and the presence and development of genotypic resistance was assessed in 41 HIV-infected patients on HAART. Four adherence parameters (drug taking adherence, dosing adherence, timing adherence and drug holidays) were scored prospectively using electronic event monitoring. Genotypic resistance at baseline and after therapy failure was scored retrospectively and a genotype-based susceptibility score was calculated. Overall median adherence rates were high. All adherence parameters were better in virological responders (n=31) compared to non-responders (n=10), drug taking adherence and number of drug holidays being significantly different. Responders had a significantly higher susceptibility score. Stepwise logistic regression showed that the number of drug holidays and a low susceptibility score were highly predictive for therapy failure. Despite the presence of a limited number of baseline resistance mutations, perfectly adherent patients can control virus replication for a prolonged period.     

Social networks of substance users with HIV infection: application of the Norbeck Social Support Scale

The role of social support networks in medication adherence among HIV-infected substance users remains understudied. In this secondary data analysis, the authors sought to determine the relationship between social support networks and antiretroviral adherence among HIV-infected substance abusers receiving methadone. They analyzed data collected in a 24-week study of 76 methadone-maintained, HIV-infected substance abusers randomized to directly observed antiretroviral therapy or treatment as usual. The authors used logistic regression to examine the relationship between social support networks and self-reported antiretroviral adherence. Their results showed that study participants had an average of 1.36 social network members (SD = 1.4); 34% of participants had at least one drug user and 25% had at least one HIV-infected person in their network. The presence of network drug users and HIV-infected network members was associated with less antiretroviral medication adherence (p < .05). The authors conclude that both social network density and characteristics of network members have implications for medication adherence.     

The pharmacology of antiretroviral drugs in pediatric patients

Background: Research has demonstrated the benefits of antiretroviral therapy in children, but problems still exist with drug therapy in this population. Although the pathogenesis of human immunodeficiency virus (HIV) infection and the general virologic and immunologic principles underlying the use of antiretroviral therapy are similar for all patients infected with HIV, there are unique considerations for HIV-infected infants, children, and adolescents. These include changes in pharmacokinetic parameters due to the continuing development and maturation of organ systems involved in drug metabolism and clearance.Objective: This review addresses pediatric pharmacologic characteristics and their effects on specific antiretroviral drugs used in neonates, infants, and children.Methods: A search of the literature from January 1983 through December 2001 was performed on MEDLINE using the search terms children, neonates, HIV, and pharmacokinetics. Relevant book chapters and conference presentations were also included.Results: The use of antiretroviral drugs in the perinatal period to reduce the risk of HIV transmission during this time poses particular problems. These include the need to modify doses due to physiologic changes in neonates, the potential for adverse short- or long-term effects on the fetus and newborn, and the efficacy of therapy at reducing the risk of perinatal transmission. The plasma concentrations and clearance rates of antiretroviral drugs in children differ from those seen in adults, but only limited data are available.Conclusions: Clinical trials are still needed to determine the optimal dosing schedules of antiretroviral drugs in all age groups. Until such trials are completed, the monitoring of plasma antiretroviral drug concentrations is necessary to assess efficacy and prevent toxicity in neonates, infants, and children.     

艾滋病患者抗病毒治疗依从现状的调查分析

目的 调查我国某农村地区艾滋病患者抗病毒治疗的服药依从性现状,并分析影响服药依从性的相关因素.方法 采用问卷对安徽省阜阳市70例艾滋病患者进行匿名调查,内容包括患者服药情况及其社会人口学资料、治疗情况、副反应、服药知识.采用SPSS 13.0统计软件对数据进行整理分析.结果 70例患者过去4 d内服药依从率为50%～100%,平均85.51%,服药依从(服药依从率≥95%)的患者占42.9%.患者漏服药物的主要原因包括外出或干农活而不在家、忘记、怕被注意到服药和应服药时睡着了.经分析发现,患者的年龄、子女个数和服药知识是影响其服药依从性的相关因素.结论 所调查艾滋病患者抗病毒治疗的服药依从性为中等水平,有待于进一步提高.针对患者漏服药物的常见原因和主要相关因素,可通过对患者提醒、督导,提高和改善患者的服药知识,从而提高艾滋病患者的服药依从性,保证其治疗效果并促进艾滋病治疗和预防工作.     

Hyperhomocysteinaemia and folate deficiency in human immunodeficiency virus-infected children

BACKGROUND: Our aim was the detection of possible deficiencies of folate and cobalamin by the measurement of plasma total homocysteine (tHcy) in 69 human immunodeficiency virus (HIV) -infected children on antiretroviral treatment. We studied the relationship of these vitamins and methionine with tHcy values. MATERIALS AND METHODS: Plasma tHcy was determined by high-performance liquid chromatography with fluorescence detection, folate and cobalamin by competitive protein-binding chemiluminescence, and methionine by ion exchange chromatography. RESULTS: Significant differences were observed between tHcy concentrations in the HIV-infected patients and the reference values for children of similar ages (P < 0.0001). Folate values were significantly lower in HIV-infected children compared with our reference paediatric population (P < 0.0001), but cobalamin concentrations were similar between patients and reference values. A significantly negative correlation was found between tHcy and folate (r = - 0.596; P < 0.0001), and a significantly positive correlation between folate and the methionine : tHcy ratio (r = 0.501; P < 0.0001). Plasma tHcy was significantly higher (P = 0.008), while folate values and methionine : tHcy ratios were significantly lower (P = 0.007 and P = 0.042), in patients on protease inhibitor treatment than in patients on other antiretroviral therapies. CONCLUSIONS: The hyperhomocysteinaemia and low methionine : tHcy ratios observed in our group of HIV-infected children are probably a consequence of the low folate values, which interfere in the remethylation of homocysteine to methionine. Patients on protease inhibitor treatment showed significantly higher plasma tHcy concentrations, and lower folate values and methionine : tHcy ratios, compared with patients on other antiretroviral therapies. Hyperhomocysteinaemia is associated with the risk of premature stroke, which may have adverse consequences in the evolution of disease.     

Carbamazepine--indinavir interaction causes antiretroviral therapy failure

OBJECTIVE: To report a case of antiretroviral therapy failure caused by an interaction between carbamazepine and indinavir. CASE SUMMARY: A 48-year-old HIV-positive white man was treated with antiretroviral triple therapy, consisting of indinavir, zidovudine, and lamivudine. His HIV-RNA (viral load) became undetectable (<400 copies/mL) less than two months after this therapy was started; this was confirmed one month later. Shortly after the start of antiretroviral therapy, the patient developed herpes zoster, which was treated with famciclovir. Tramadol was initially prescribed for postherpetic neuralgia; however, this was substituted with carbamazepine due to insufficient analgesic effect. Indinavir plasma concentrations decreased substantially during carbamazepine therapy. Carbamazepine was stopped after 2.5 months and, two weeks later, the HIV-RNA was detectable (6 x 103 copies/mL). Resistance for lamivudine was observed in that blood sample; resistance for zidovudine might have been present, and resistance to indinavir was not detected. A few months later, a further increase of the HIV-RNA occurred (300 x 103 copies/mL), after which the therapy was switched to a new antiretroviral regimen containing nevirapine, didanosine, and stavudine. DISCUSSION: Physicians may prescribe carbamazepine for HIV-infected patients to treat seizures or postherpetic neuralgia, which are complications of opportunistic infections such as herpes zoster or toxoplasmosis. Carbamazepine is a potent enzyme inducer, predominantly of the CYP3A enzyme system, while HIV-protease inhibitors such as indinavir are substrates for and inhibitors of CYP3A. Therefore, an interaction between these drugs could be expected. A low dose of carbamazepine (200 mg/d) and the usual dose of indinavir (800 mg q8h) in our patient resulted in carbamazepine concentrations within the therapeutic range for epilepsy treatment; indinavir concentrations dropped substantially. The virologic, resistance, and plasma drug concentration data, as well as the chronology of events, are highly indicative of antiretroviral treatment failure due to the interaction between carbamazepine and indinavir. CONCLUSIONS: Concomitant use of carbamazepine and indinavir may cause failure of antiretroviral therapy due to insufficient indinavir plasma concentrations. Drugs other than carbamazepine should be considered to prevent this interaction. Amitriptyline or gabapentin are alternatives for postherpetic neuralgia; valproic acid or lamotrigine are alternatives for seizures. When alternate drug therapy is not possible, dosage adjustments, therapeutic drug monitoring, and careful clinical observation may help reduce adverse clinical consequences.     

Lopinavir/ritonavir exposure in treatment-naive HIV-infected children following twice or once daily administration

OBJECTIVES: Lopinavir/ritonavir is approved for treatment of HIV-infected children at a dosage regimen of 230/57.5 mg/m(2) twice daily. However, once daily administration could increase convenience and patient adherence. Our study aimed at evaluating whether inhibitory concentrations are maintained in plasma following administration of lopinavir/ritonavir once daily. PATIENTS AND METHODS: Lopinavir/ritonavir was administered at the standard twice daily regimen to 21 HIV-infected children, as a component of their antiretroviral treatment. Following at least 1 month of administration, seven patients received a dose of 460/115 mg/m(2) once daily for three consecutive days. After the third dose of once daily administration, blood samples were drawn at the following times: 0 (pre-dose), 1, 2 and 4 h following administration. The pre-dose (C(min)) and the peak (C(max)) concentrations were compared with the values obtained following twice daily administration in all the study patients. RESULTS: Median (interquartile range) C(min) with the once daily regimen was 1.59 (0.77-6.85) mg/L versus 7.90 (5.45-9.77) mg/L with the twice daily regimen (P < 0.05). C(min) was considered inhibitory for wild-type virus (>1.0 mg/L) in four out of seven patients. C(max) did not differ significantly between the once daily and twice daily regimens. CONCLUSIONS: Our small pilot study suggests that lopinavir/ritonavir once daily may be a suitable regimen for antiretroviral-naive children. However, due to the high interindividual variability and low concentrations in some patients, therapeutic drug monitoring may be necessary to ensure that concentrations are adequate to inhibit viral replication. A formal clinical study of lopinavir/ritonavir once daily in treatment-naive children is warranted.     

Comparison of plasma,saliva, and hair lamotrigine concentrations

BackgroundIn some clinical situations (pregnancy, aging, drug resistance, toxicity), measurements of lamotrigine plasma levels may be reliable. Limited studies indicate that saliva and hair could be alternative sources for monitoring lamotrigine therapy. The drug content in hair can also be used to assess the history of drug therapy and to ascertain long-term patient compliance. The aims of this study were to 1) determine the correlations among plasma, saliva, and hair lamotrigine concentrations, 2) evaluate saliva as an alternative matrix for monitoring drug levels and 3) evaluate hair as a source of information on adherence to antiepileptic treatment and on the correlation of hair concentrations with clinical outcomes in patients with epilepsy.MethodsPlasma, saliva, and hair lamotrigine concentrations were measured by liquid chromatography–tandem mass spectrometry in positive ionization mode. The study group (n = 85) was recruited among the epileptic patients at the Institute of Psychiatry and Neurology, Warsaw, Poland.ResultsPlasma concentrations were not influenced by sex, age, or the concomitant use of other antiepileptic drugs. Lamotrigine saliva and plasma concentrations were strongly correlated (r = 0.82, p < 0.001). Lamotrigine hair concentrations were correlated with the plasma concentrations (r = 0.53, p < 0.001) and daily dose in mg/kg (r = 0.23, p = 0.024). The analysis revealed no significant correlation between lamotrigine hair levels and the number of seizures in the previous 3 months (r = -0.1, p > 0.05).ConclusionsThe lamotrigine saliva concentration is strongly correlated with its plasma level, and saliva can be used as an alternative matrix to plasma for monitoring. Lamotrigine can also be successfully measured in hair, and the drug levels in hair tend to be correlated with the levels in plasma. However, lamotrigine levels in hair may not correspond to clinical outcomes (i.e., seizure episodes).     

Steady-state pharmacokinetics of tenofovir-based regimens in HIV-infected pediatric patients

HIV-infected children are treated with tenofovir in combination with other, potentially interacting, antiretroviral agents. We report the pharmacokinetic parameters of tenofovir in combination with efavirenz, darunavir-ritonavir, or atazanavir-ritonavir in HIV-infected children. HIV-infected patients 8 to 18 years of age receiving a tenofovir (300 mg)-based regimen containing efavirenz (300 or 600 mg) once daily (group 1), darunavir (300 or 600 mg)-ritonavir (100 mg) twice daily (group 2), or atazanavir (150 to 400 mg)-ritonavir (100 mg) once daily (group 3) were enrolled. Plasma samples were collected over a 24-h time interval. The 90% confidence intervals (90% CI) of the geometric means for the area under the plasma concentration-time curve (AUC) and the minimum concentration of drug in serum (C(min)) of each antiretroviral were computed and checked for overlap with intervals bracketing published values obtained in adult or pediatric studies demonstrating safety and/or efficacy. Group 1 efavirenz plasma concentrations were observed to be higher in patients receiving fixed-dose combination tablets compared with subjects receiving the individual formulation. In group 2, tenofovir and darunavir exposure was observed to be lower than expected. In group 3, tenofovir and atazanavir administered concomitantly produced exposures similar to those published for adult patients. The 90% CI of AUC and C(min) for tenofovir overlapped the target range for all combinations. Informal comparisons of treatment groups did not indicate any advantage to any combination with respect to tenofovir exposure. Further study of exposures achieved with antiretrovirals administered in combination is warranted.