主题：【求助】急需的文献，哪位能帮忙找到全文！

不知是你的页码错了，还是这不是你要找的。很遗憾我载不了全文。

Title: Clinical pharmacokinetics of lamivudine
Author(s): Johnson MA, Moore KHP, Yuen GJ, Bye A, Pakes GE
Source: CLINICAL PHARMACOKINETICS 36 (1): 41-66 JAN 1999
Document Type: Review
Language: English
Cited References: 69      Times Cited: 65       
Abstract: Lamivudine (3TC), the negative enantiomer of 2'-deoxy-3'-thiacytidine, is a dideoxynucleoside analogue used in combination with other agents in the treatment of human immunodeficiency virus type 1 (HIV-1) infection and as monotherapy in the treatment of hepatitis B virus (HBV) infection. Lamivudine undergoes anabolic phosphorylation by intracellular kinases to form lamivudine 5'-triphosphate, the active anabolite which prevents HIV-1 and HBV replication by competitively inhibiting viral reverse transcriptase and terminating proviral DNA chain extension.
The pharmacokinetics of lamivudine are similar in patients with HIV-1 or HBV infection, and healthy volunteers. The drug is rapidly absorbed after oral administration, with maximum serum concentrations usually attained 0.5 to 1.5 hours after the dose. The absolute bioavailability is approximately 82 and 68% in adults and children, respectively. Lamivudine systemic exposure, as measured by the area under the serum drug concentration-time curve (AUC), is not altered when it is administered with food.

Lamivudine is widely distributed into total body fluid, the mean apparent volume of distribution (Vd) being approximately 1.3 L/kg following intravenous administration. In pregnant women, lamivudine concentrations in maternal serum, amniotic fluid, umbilical cord and neonatal serum are comparable, indicating that the drug diffuses freely across the placenta. In postpartum women lamivudine is secreted into breast milk. The concentration of lamivudine in cerebrospinal fluid (CSF) is low to modest, being 4 to 8% of serum concentrations in adults and 9 to 17% of serum concentrations in children measured at 2 to 3 hours after the dose. In patients with normal renal function, about 5% of the parent compound is metabolised to the trans-sulphoxide metabolite, which is pharmacologically inactive.

In patients with renal impairment, the amount of trans-sulphoxide metabolite recovered in the urine increases, presumably as a function of the decreased lamivudine elimination. As approximately 70% of an oral dose is eliminated renally as unchanged drug, the dose needs to be reduced in patients with renal insufficiency. Hepatic impairment does not affect the pharmacokinetics of lamivudine. Systemic clearance following single intravenous doses averages 20 to 25 L/h (approximately 0.3 L/h/kg). The dominant elimination half-life of lamivudine is approximately 5 to 7 hours, and the in vitro intracellular half-life of its active 5'-triphosphate anabolite is 10.5 to 15.5 hours and 17 to 19 hours in HIV-1 and HBV cell lines, respectively.

Drug interaction studies have shown that trimethoprim increases the AUC and decreases the renal clearance of lamivudine, although lamivudine does not affect the disposition of trimethoprim. Other studies have demonstrated no significant interaction between lamivudine and zidovudine or between lamivudine and interferon-alpha-2b. There is limited potential for drug-drug interactions with compounds that are metabolised and/or highly protein bound.

KeyWords Plus: IMMUNODEFICIENCY-VIRUS INFECTION; HEPATITIS-B-VIRUS; ZIDOVUDINE COMBINATION THERAPY; CD4 CELL COUNTS; HIV-INFECTION; REVERSE-TRANSCRIPTASE; CUBIC MILLIMETER; PHASE I/II; 2'-DEOXY-3'-THIACYTIDINE BCH-189; (-)-2'-DEOXY-3'-THIACYTIDINE 3TC
Addresses: Johnson MA (reprint author), Glaxo Wellcome Res & Dev Inc, Dept Clin Pharmacol, Greenford Rd, Greenford UB6 0HE, Middx England
Glaxo Wellcome Res & Dev Inc, Dept Clin Pharmacol, Greenford UB6 0HE, Middx England
Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA

E-mail Addresses: maj@glaxowellcome.co.uk
Publisher: ADIS INTERNATIONAL LTD, 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND
Subject Category: PHARMACOLOGY & PHARMACY
IDS Number: 162WG

ISSN: 0312-5963

原文由 wanghf0821 发表:
不知是你的页码错了，还是这不是你要找的。很遗憾我载不了全文。

谢谢了。
不过我的页码没错的，这篇文章是在增刊里的，“Supplement 1”。

Title: The low potential for drug interactions with zanamivir
Author(s): Daniel MJ, Barnett JM, Pearson BA
Source: CLINICAL PHARMACOKINETICS 36: 41-50 Suppl. 1, 1999
Document Type: Review
Language: English
Cited References: 11      Times Cited: 14       
Abstract: Objective: The objective of this study was to assess the potential of zanamivir, a specific inhibitor of influenza A and B virus neuraminidase, to interact with other coadministered therapies in the clinical setting.
Design: Potential interactions with zanamivir were examined in a series of in vitro and in vivo model systems.

Interventions: The expression of microsomal cytochrome P450 (CYP) isoenzymes was examined after daily treatment of rats with intravenous zanamivir. The ability of zanamivir to inhibit the metabolism of CYP probe substrates was studied in human liver microsomes. The binding of zanamivir to human and animal red blood cell fractions and plasma proteins was measured. Finally, the effect of commonly coadministered drugs on the ability of zanamivir to inhibit viral replication in vitro was tested.

Results: Zanamivir had no effect on the expression of microsomal CYP isoenzymes after daily intravenous treatment of rats with zanamivir 1, 9 or 90 mg/kg for 5 weeks. Zanamivir at concentrations up to 500 mu mol/L (150 mg/L) had no effect on the metabolism of the CYP probe substrates bufuralol, chlorzoxazone, coumarin, ethoxyresorufin, mephenytoin, midazolam, phenacetin and tolbutamide by human liver microsomes. The binding of zanamivir 0.05 to 10 mg/L to human, dog and rat red blood cells and plasma proteins was low. The in vitro potency of zanamivir against influenza virus in Madin Darby canine kidney cells was not adversely affected by aspirin (acetylsalicylic acid) 1.2 mmol/L, paracetamol (acetaminophen) 6.6 mmol/L, ibuprofen 243 mu mol/L, phenylephrine 6 mmol/L, oxymetazoline 350 mu mol/L, promethazine 35 mu mol/L and co-amoxiclav (amoxicillin-clavulanic acid) 1.66 mmol/L.

Conclusions: These data suggest the following: (i) there is no theoretical basis for expecting metabolic interactions between zanamivir and other coadministered compounds; (ii) zanamivir is unlikely to interact with coadministered compounds that are protein bound; and (iii) commonly coadministered drugs will not interfere with the antiviral activity of zanamivir in vivo. Although none of these in vitro, or in vivo studies were exhaustive, and although none were performed in humans, all the data are consistent with zanamivir having a very low potential for interactions with coadministered drugs in the clinical setting.

Addresses: Daniel MJ (reprint author), Glaxo Wellcome Res & Dev Ltd, Bioanal & Drug Metab Div, Priory St, Ware SG12 0D5, Herts England
Glaxo Wellcome Res & Dev Ltd, Bioanal & Drug Metab Div, Ware SG12 0D5, Herts England

Publisher: ADIS INTERNATIONAL LTD, 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND
Subject Category: PHARMACOLOGY & PHARMACY
IDS Number: 222RC

ISSN: 0312-5963

还是只有摘要，无能为力了！

我有一个办法可以搞到这个文献, 但是授人以鱼不如授人以渔.
所以, 方法是这样的: 给作者写个E-mail, 请他给你send a copy.
油箱我帮你搜了一下: danielje@hawaii.edu, 通常隔天你就能得到回应了.
实践证明这个方法很不错, 老外通常都很kind, 有时还会给你推荐讨论类似问题的其它文献, 如果文献很老了, 他们会给你邮寄hard-copy. 当然你这个是99年的, 应该有电子版.
试试吧, 希望对其他朋友也有帮助!
PS: 楼主分好多哦, 我看到你在文献版也发了悬赏帖了! 我在那边跟了, 但是也决不能放过这个赚分的机会哦, So, 再跟一遍! 多谢支持!

原文由 gpdx 发表:
油箱我帮你搜了一下: danielje@hawaii.edu, 通常隔天你就能得到回应了.

谢谢，你确信这个邮箱正确吗？