Cocktail dosing

Hakala, K. et al., Development of LC/MS/MS methods for cocktail dosed Caco-2 samples using atmospheric pressure photoionization and electrospray ionization, Anal. Chem., 75, 5969, 2003. 

Efavirenz is given orally at a dose of one 600-mg tablet per day. As an important part of the AIDS cocktail, efavirenz is administered with the same protease inhibitors and NRTIs as described in the nevirapine section. The half-hfe of efavirenz after a single dose is 52-76 h, and multiple doses lower the half-life to 40-55 h. Treatment with efavirenz has been associated with the development of serious psychiatric side-effects, including severe depression, suicidal thoughts, aggressive behavior, and paranoid and manic reactions. 

Other factors add to the problem. Starchy foods on menus are often less expensive. Specials are often tempting, but may not fit the diet. And a cocktail ahead of time can cause one to make food choices with wild abandon. Cafeterias have the advantage of offering a wide selection, which permits a person to adhere to his or her diet. But it is essential to have a dose of self discipline as an appetizer while standing in fine. 

Various triggers can cause MCS to develop. At the moment, the best-known causes are long-term (over many years) exposure to a cocktail of various, often low doses of chemical substances and/or a one-time exposure to a high dose of chemical substances, such as formaldehyde, solvents, pesticides, insecticides, toluene, liquid narcotics and other chemical substances. Two examples are 9/11 rescue workers and GulfWar veterans. 

In reality psychiatric patients are often prescribed a whole cocktail of drugs, often at high doses. Many take a combination of neuroleptics, so-called mood stabilisers and benzodiazepines, all of which have sedative effects that dampen down and restrict nervous system activity in different ways. A British government report published in 2007 suggested that up to one in three psychiatric patients was being overtreated with drugs... 

The application of APCI-LC/MS techniques for the rapid determination of protein binding and pharmacokinetics in drug discovery were recently described by Allen et al. using a single quadrupole instrument. " A cocktail approach consisted of four experimental compounds and a control compound dosed orally at 1 mg/kg with plasma samples obtained at 0.5, 1, 2, 4, and 8h post dose. To insure reproducibility, the control compound was tested with each cocktail. This approach generated timely systemic exposure (AUC and Cmax) data on 44 test compounds in three work days, using two laboratory scientists. 

---