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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.

StatPearls [Internet].

Show detailsTreasure Island (FL): StatPearls Publishing; 2025 Jan-.Search term Loading Dose

Anthony Miniaci; Vikas Gupta.

Author Information and Affiliations

Authors

Anthony Miniaci; Vikas Gupta1.

Affiliations

1 Wellness Psychiatry P.C

Last Update: June 5, 2023.

Definition/Introduction

Loading doses are a means to quicks achieve therapeutic drug concentrations or prompt an immediate clinical response. Loading doses are larger than maintenance doses and are usually administered as a single bolus, although some drugs (eg, amiodarone or digoxin) may require multiple loading doses administered over several hours to days.[1] An intravenous loading dose of phenytoin, on the other hand, should be administered as a single dose. Medications with shorter half-lives (eg, heparin for treating pulmonary embolism) may also require a loading dose to achieve their therapeutic effect immediately.

In medicine, the treatment for most conditions uses various pharmacological medications. For each of these individual medications, the route of administration, appropriate dosage, and frequency of use are determined by the medication’s pharmacokinetics (PK). Pharmacokinetics is the relationship between an administered dose of a drug and its measured concentration within the body. An individual medication’s PK is governed by how it moves within the body through absorption, bioavailability, distribution, metabolism, and excretion.

The characteristics that define an individual medication’s PK can help determine the loading dose. While a patient takes a specific drug to achieve the therapeutic benefit, the drug must reach a certain steady-state concentration.[2] Typically, for any medication, five to seven half-lives are required for this to be achieved.

Table

Reaching this concentration is typically not an issue for drugs with short half-lives; however, other medications or conditions may require a more rapid therapeutic onset. For instances where a therapeutic steady-state concentration is needed immediately, loading doses can be utilized to achieve this therapeutic concentration more rapidly.[2]

A loading dose is typically calculated through the following formula:

LD=(Volume of Distribution X Steady State Concentration)/(Bioavailability X Drug Fraction of Salt Form that is Active Drug)

For this formula, concentration steady-state is defined as the therapeutic concentration of medication in the body, while bioavailability is the fraction of an administered dose that reaches systemic circulation. For intravenous drugs, the bioavailability = 1 because the drug is injected directly into the bloodstream. For orally administered drugs, the bioavailability will be affected by several factors, including first-pass metabolism, absorption, etc). The volume of distribution is typically calculated as follows:

Vd=Dose of Medication Given/Concentration in the Plasma

The calculation of the loading dose should not be confused with the maintenance dose, which is the dose required to maintain steady-state concentration. This calculation is: 

MD=(Concentration Steady State X Clearance X Dosing Interval)/Bioavailability

Clearance can be determined using the known half-life of a medication, which is the time required for a dose to reach 50% of its initial plasma concentration. Clearance can ultimately be determined through the following: 

CL=(0.693 X Vd)/ Half-life

Issues of Concern

When prescribing a loading dose of a new medication, there are many factors that a clinician must consider. Through the formulas above, the loading dose of any drug is influenced by many of the pharmacokinetic variables. Loading doses are challenging to calculate, as they necessitate multistep calculations utilizing patient data (such as weight) and the specific drug (eg, the estimated volume of distribution or drug half-life). Staff may mistakenly continue loading doses instead of lowering to maintenance doses, particularly when patients transfer between care settings (such as from the emergency department to being admitted to the floor or at discharge from the hospital back to outpatient status).

Bioavailability is typically affected by the route of administration of the medication. Each medication typically has a route of administration that provides the best bioavailability. For example, in one study, researchers found that sublingual administration of misoprostol had significantly higher bioavailability than oral administration.[3] 

Higher bioavailability allows for the utilization of a lower loading dose to reach the same steady-state concentration, leading to better medication safety and efficacy. Patient comorbidities can also affect medication bioavailability. For example, celiac disease causes atrophy of the duodenal villi, which can hinder the absorption and bioavailability of medications given orally. As a result, other drugs have been developed to allow proper treatment for these patients, such as a medication to increase iron absorption in patients with celiac disease and iron deficiency anemia.[4]

Further, various physiological factors can affect the concentration and pharmacokinetics of medication. One study found that the clearance of ciprofloxacin significantly decreases with age and worsening kidney function.[5] Failure to adjust for these factors could lead to toxicity or other related side effects. Ultimately, it is essential to consider all factors while dosing medications, as any change in these variables, will inevitably affect the loading dose and, consequently, steady-state concentration.

Clinical Significance

A medication’s loading dose has many vital clinical applications. In emergencies, drugs must reach therapeutic concentration rapidly, often requiring a loading dose. For example, studies have found that a loading dose of levetiracetam is essential for adequate treatment of status epilepticus.[6] Loading doses require 

Also, knowing factors that may affect a medication’s loading dose is imperative to pharmacological treatments for chronic conditions. For example, initiation of dofetilide for treating atrial fibrillation requires an initial loading dose before reaching therapeutic concentrations. As a clinician administers this medication, they must monitor creatinine clearance and QTc interval length and adjust the dosage accordingly to avoid potentially deadly side effects such as ventricular tachycardia.[7]

Nursing, Allied Health, and Interprofessional Team Interventions

Using pharmacological therapy to treat a patient's underlying condition is common in today's medical field. Although these therapies can be beneficial, they can also cause significant harm to the patient. One study found that almost 11% of prescriptions have errors, and 16% of these errors result in harm to the patient.[8] This situation makes it essential that dosing medications are done with an interprofessional team to ensure efficacy and safety. Ways to help facilitate this would be by:

• Having an open line of communication between all clinicians and specialties – this is especially true in instances of transition of care
• Ensure clinicians and pharmacists work together to ensure proper dosing and medication choice
• Order drug blood concentrations when clinically appropriate
• Educate family and patient about potential adverse drug reactions
• Ensure appropriate specialties are involved with the care of a patient when deemed appropriate
• Computerized prescribing and order entry systems should have dosing checks to flag potential dosing errors and offer recommendations for correct dosing.

Interprofessional efforts become even more essential when a situation with a patient becomes more critically ill, requiring higher levels of care. By working in an interprofessional team, patient outcomes can improve, and medication errors can be avoided.[9] [Level 4]

Review Questions

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• Comment on this article.

References

1.Haffajee CI, Love JC, Canada AT, Lesko LJ, Asdourian G, Alpert JS. Clinical pharmacokinetics and efficacy of amiodarone for refractory tachyarrhythmias. Circulation. 1983 Jun;67(6):1347-55. [PubMed: 6851030]2.Fan J, de Lannoy IA. Pharmacokinetics. Biochem Pharmacol. 2014 Jan 01;87(1):93-120. [PubMed: 24055064]3.Amini M, Reis M, Wide-Swensson D. A Relative Bioavailability Study of Two Misoprostol Formulations Following a Single Oral or Sublingual Administration. Front Pharmacol. 2020;11:50. [PMC free article: PMC7029744] [PubMed: 32116725]4.Giancotti L, Talarico V, Mazza GA, Marrazzo S, Gangemi P, Miniero R, Bertini M. Feralgine™ a New Approach for Iron Deficiency Anemia in Celiac Patients. Nutrients. 2019 Apr 20;11(4) [PMC free article: PMC6520849] [PubMed: 31009990]5.Gai X, Shen N, He B, Zhou Q, Bo S, Li X, Zhai S, Yin A, Lu W. [Population pharmacokinetics of ciprofloxacin in Chinese elderly patients with lower respiratory tract infection]. Zhonghua Yi Xue Za Zhi. 2015 May 26;95(20):1581-5. [PubMed: 26463606]6.Rösche J, Dudek M, Teleki A, Godau J, Bösel J. [Levetiracetam for treatment of status epilepticus - an update]. Fortschr Neurol Psychiatr. 2019 Jun;87(6):357-363. [PubMed: 31261415]7.Torp-Pedersen C, Brendorp B, Køber L. Dofetilide: a class III anti-arrhythmic drug for the treatment of atrial fibrillation. Expert Opin Investig Drugs. 2000 Nov;9(11):2695-704. [PubMed: 11060831]8.Fitzgerald RJ. Medication errors: the importance of an accurate drug history. Br J Clin Pharmacol. 2009 Jun;67(6):671-5. [PMC free article: PMC2723207] [PubMed: 19594536]9.Bakker T, Klopotowska JE, de Keizer NF, van Marum R, van der Sijs H, de Lange DW, de Jonge E, Abu-Hanna A, Dongelmans DA., SIMPLIFY Study Group. Improving medication safety in the Intensive Care by identifying relevant drug-drug interactions - Results of a multicenter Delphi study. J Crit Care. 2020 Jun;57:134-140. [PubMed: 32145656]

Disclosure: Anthony Miniaci declares no relevant financial relationships with ineligible companies.

Disclosure: Vikas Gupta declares no relevant financial relationships with ineligible companies.

Copyright © 2025, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

Bookshelf ID: NBK557418PMID: 32491350 Share

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• Cite this PageMiniaci A, Gupta V. Loading Dose. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.

In this Page

• Definition/Introduction
• Issues of Concern
• Clinical Significance
• Nursing, Allied Health, and Interprofessional Team Interventions
• Review Questions
• References

Related information

• PMCPubMed Central citations
• PubMedLinks to PubMed

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