Do all drugs need to achieve the steady state concentration after 4-5 half life in order to see the therapeutic effect ? Doesn't ibuprofen produce its effect from a single dose without 4-5 half life ?
Half life is the time duration required by a drug to get reduced in plasma by half of its initial concentration. For example if the plasma concentration is 100mg now what time it will take to remain 50 mg then 25mg and so on. A drug needs 4-5 half life toget elliminated or excreted completely from body not to acheive a steady state . Actually steady state is an equlibrium mantained by frequent doses of drugs. A single dose may acheive a minimum effective concentration in plasma and effects will be observed but a single dose will not acheive the steady state concentration.
Half life is the time duration required by a drug to get reduced in plasma by half of its initial concentration. For example if the plasma concentration is 100mg now what time it will take to remain 50 mg then 25mg and so on. A drug needs 4-5 half life toget elliminated or excreted completely from body not to acheive a steady state . Actually steady state is an equlibrium mantained by frequent doses of drugs. A single dose may acheive a minimum effective concentration in plasma and effects will be observed but a single dose will not acheive the steady state concentration.
Mostafa. Your question implies that the drug effect would be seen only when plasma levels exceed a minimally effective level for a certain time. If dependent on plasma levels it must appear as soon as that level is exceeded, ie after the initial peak. Therefore your question seems to be really about the possibility of a drug effect being achieved when the duration of a minimum effective concentration is sufficient. There will be conditions where it takes time for a drug effect to become evident ( even if it begins immediately) and then the duration would be crucial. That could apply to ibuprofen where it takes time for it to produce a clinically appreciable benefit in a large joint like a knee for example. There will be many others, affected by different individual conditions, such as the severity of the condition being treated in a particular patient. Arguably, your question could apply to antibiotics where such a concentration needs to be sustained to kill any bacteria that survive or emerge after the initial peak concentration. That means it does also depend upon how the beneficial effect is defined.
Andrew Sutton & Ashique Ali with your answer i am also agree. But sir in practice im also getting such difficulties. for example one patient is taken for heart transplant but antimicrobial is used outside recommendation . Now in that case we always confused to suggest time gap between two antibiotics if surgery prolonged??
Please answer if possible??
The best treatment will depend upon several local conditions, in particular the exact strain or strains of bacteria that are considered a risk by your local bacteriologist as that will determine which antibiotic is effective. A heart transplant requires a whole team so you need to consult with the person or persons in the team who have the relevant information.
Yes, all drugs will reach stead-state level at 4-5 half-lives if they undergo first order kinetics. Zero-order kinetic drugs are eliminated differently. In the case of ibuprofen, it has a really short half-life so it needs to be given frequently in a day to reach a steady state concentration that you want. Giving another NSAID with a longer half-life would be a better option to do away with frequent dosing.
Sorry, But I'm not getting this. Isn't Css the same as the plasma therapeutic level ? Because if so, in the case of Acetaminophen, just one dose of 500 mg would reach the Css, and there would be no need for 4-5 half life ?
The key is dosing at the same interval as the half life. Then steady state is achieved at a minimum of 5 half lives. It helps to draw it out on graph paper.
Dr.Andrew, if we want to reach the Css from one dose(Loading dose), we will use this equation Dose (Oral)=Vd*Css divided by the Bioavailability. Here are the info. The volume of distribution is about 70 L for someone who weigh 70 K.g and the oral bioavailability is about 70%, and the therapeutic level is 10 to 20 mcg/mL so a simple calculation would yield 500 mg to be the dose which is common in practice. So, how is this possible ? Aren't we suppose to reach the Css after 4-5 half life, not just from one dose ? Am I getting this right ? Or there is a difference between the therapeutic level and the Css ?
The time required to reach steady state depends on the elimination half-life of the drug, defined as the time required for the serum drug concentration to decrease by 50%. The time required for these drugs to reach a steady state may differ from the conventional 5 half-lives.
Once steady state has been reached, peak and/or trough serum samples may be collected after the next scheduled dose. For peak samples, that would typically be 2 to 3 hours after an oral dose,2 30 to 60 minutes after an intravenous dose,2 2 to 4 hours after an intramuscular dose,2 or 1 to 1.5 hours after an intranasal dose.4,5 Trough samples are drawn just before administration of the next scheduled dose. TDM of aminoglycoside antibiotics, such as gentamicin and amikacin, requires determination of both peak and trough concentrations for multiple daily dosing regimens.3 Only trough concentrations are measured for most other drugs.
References
1. Pippenger CE. Principles of therapeutic drug monitoring. In: Wong SHY, ed. Therapeutic Drug Monitoring and Toxicology by Liquid Chromatography. Boca Raton, FL: CRC Press; 1985:11-36.
2. Garg U, Jacobs DS, Grady HJ, et al. Therapeutic drug monitoring. In: Jacobs DS, Oxley DK, Demott WR, eds. Jacobs & Demott Laboratory Test Handbook. 5th ed. Cleveland, Ohio: Lexi-Comp, Inc; 2001:731-771.
3. Moyer TP, Shaw LM. Therapeutic drugs and their management. In: Burtis C, Ashwood E, Bruns D, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. Philadelphia, PA: Saunders; 2005:1237-1280.
Who mentioned that a steady state needs to be reached before seeing a therapeutic effect?
Dear All. Lets be clear that the shortest time to steady state is achieved by 5 doses given at the same intervals as the half life. Longer intervals will produce proportionally lower steady state concentrations provided no other compartment effect exists such as saturation of protein binding. Large loading doses of antibiotics are used to provide longer durations of levels above the MIC of the target organism. It does not aim at steady state which cannot be achieved after 1 dose by definition.
@Mostafa Elsersy, to re-inforce Dr Sutton's comment; the Therapeutic level (I've also seen MEC, Minimum Effective Concentration); is not necessarily the same as the Steady-state concentration. The latter in an individual is dependent on the amount and frequency of dosing, as well as the drug's intrinsic clearance; your understanding of the drug's PK will allow you to adjust the dosing regimen to reach and maintain a target concentration, for instance the use of loading doses for antibiotics in acute cases.
Css and therapeutic range are not exactly synonymous. You can achieve a plasma concentration within the therapeutic range with a single dose, then it will drop back to less than MEC after each dose; however, when in steady-state, the plasma concentration of the drug at anytime will always be within the therapeutic range. This is especially important when managing chronic conditions. Please take a look at the attached figures to get a clearer idea.
References: Article DESIGN AND IN VITRO EVALUATION OF DICLOFENAC SODIUM MATRIX TABLETS
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