Therapeutic Ranges

The ideal sample is that drawn at steady state just before the next dose (steady-state trough sample). Steady state is reached after an interval of 5 drug half-lives have elapsed, which for most of these drugs is less than 48 h. Exceptions to this rule have to be made for nevirapine (an NNRTI) and saquinavir (a PI), both of which have longer half-lives and should not be monitored until 4 days after initiation of the drug regimen see Table 2. Despite the fact that the majority of HIV/AIDS drugs

Table 3

High-Performance Liquid Chromatography (HPLC) versus Tandem-MS

Table 3

High-Performance Liquid Chromatography (HPLC) versus Tandem-MS

Parameters

HPLC

Tandem-MS

Sample volume

0.5-1.0 mL

0.08mL

Sensitivity

10-100 |xg/L

1 |g/L

Sample preparation

Lengthy

Just precipitation of

proteins

Chromatography time

15min-1 h

<5 min

General

Different methods needed

Universal method

for different drugs

have short-half-lives only didonosino is available in a slow release form. Most of the PIs have in vitro 95% inhibitory concentrations of approximately 100ng/mL. At Children's National Medical Center, the lower limit of the therapeutic range for the PIs is taken as 150ng/mL. For the upper limit, we recurrently recommend concentrations <6000ng/mL, except for lopinavir, which we recommend should be maintained at concentrations <12, 000ng/mL. These values are gleaned from the literature and are tentative therapeutic ranges (8,9,12,16,21-29). For the NNRTIs, we currently recommend tentative therapeutic ranges between 1200 and 7000 ng/mL. The HIV/AIDS drugs are metabolized by CYP 450,2B6,1A2,2A6,2C, and 2D6 (efavirenz, nevirapine, nelfinavir, and ritonavir) and by 3A, particularly 3A4 (indinavir, delavirdine, ritonavir, nevirapine, saquinavir, and nelfinavir).

Significant drug-drug interactions occur again, emphasizing the need for TDM. The PIs are also strongly protein-bound to a1-acid glycoprotein, which is an acute-phase reactant (98% except for indinavir 65%), raising the possibility of the need to measure free drug concentrations for this group.

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