Biopharmaceutical Considerations in Subcutaneous and Intramuscular Drug Administration

Ballard, Berton E.

doi:10.1002/jps.2600570301

Cited by 122 publications

(45 citation statements)

References 117 publications

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“…The different absorption rates from different injection sites are likely to be related to regional differences in blood and lymph flow. It has been estimated that in "active" regions of the body (e.g., deltoid), one lymphatic junction in every 2 to 5 may be open, but in "motionless" regions (e.g., buttock), there may be only one junction in 50 to 100 that is open (Ballard, 1968). Similarly, blood flow also varies in different regions of the body, with blood flow being least in the buttock, intermediate in the thigh, and greater in the deltoid region (Evans et al, 1975).…”

Section: Discussionmentioning

confidence: 99%

Lymphatic Absorption of Subcutaneously Administered Proteins: Influence of Different Injection Sites on the Absorption of Darbepoetin Alfa Using a Sheep Model

Kota¹,

Machavaram²,

McLennan³

et al. 2007

Drug Metab Dispos

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ABSTRACT:The relative contribution of the lymph and blood in the absorption of darbepoetin alfa (DA) from different s.c. injection sites was determined using a central lymph-cannulated sheep model. DA was administered to parallel groups either as a bolus i.v. injection (0.5 g/kg) into the jugular vein or as a bolus s.c. injection (2 g/kg) into the interdigital space, the abdomen, or the shoulder. In the lymph-cannulated groups, the thoracic lymph duct was cannulated for continuous collection of central lymph, and blood samples were periodically collected via the jugular vein in all the groups. The concentration of DA in serum and lymph was determined by enzyme-linked immunosorbent assay. The total fraction of the dose reaching the systemic circulation and the fractions absorbed via the lymph and the blood were determined. A pharmacokinetic model was constructed to simultaneously fit the data from all the treatment groups. Absorption was essentially complete for all three injection sites in non-lymph-cannulated s.c. groups, but the rates of absorption differed significantly. Based on the modeling results for the lymph-cannulated groups, the lymphatics represented the predominant absorption route for both the interdigital (90 ؎ 1%) and the abdomen (67 ؎ 9%) injection sites. Fluorescein isothiocyanate dextran visualization studies revealed that the lymph draining the shoulder injection site entered the thoracic lymph duct distal to the point of cannulation, effectively precluding collection of thoracic lymph from this site. For that reason, the contribution of the lymphatics following injection in the shoulder could not be determined using these cannulation procedures.

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Section: Discussionmentioning

confidence: 99%

Lymphatic Absorption of Subcutaneously Administered Proteins: Influence of Different Injection Sites on the Absorption of Darbepoetin Alfa Using a Sheep Model

Kota¹,

Machavaram²,

McLennan³

et al. 2007

Drug Metab Dispos

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“…However, drugs with a molecular weight greater than 20,000 mainly transfer to lymph nodes. 82 The commonly used class B CpG ODN with phosphorothioate backbone has a molecular weight of about 8000, and its transferability to lymph nodes is low. For therapeutic NPs administered into the abdominal cavity of mice, it has been reported that NPs with sizes of 100-200 nm are excellent for transferring to lymph nodes and in retention.…”

Section: Delivery Of Cpg Odns To Target Tissuesmentioning

confidence: 99%

Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system

Hanagata¹

2012

IJN

163

139

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Unmethylated cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) are recognized by Toll-like receptor 9 (TLR9) found in antigen-presenting cells and B cells and can activate the immune system. Using CpG ODNs as an adjuvant has been found to be effective for treating infectious diseases, cancers, and allergies. Because natural ODNs with only a phosphodiester backbone are easily degraded by nuclease (deoxyribonuclease [DNase]) in serum, CpG ODNs with a phosphorothioate backbone have been studied for clinical application. CpG ODNs with a phosphorothioate backbone have raised concern regarding undesirable side effects; however, several CpG ODNs with only a phosphodiester backbone have been reported to be stable in serum and to show an immunostimulatory effect. In recent years, research has been conducted on delivery systems for CpG ODNs using nanoparticles (NPs). The advantages of NP-based delivery of CpG ODN include (1) it can protect CpG ODN from DNase, (2) it can retain CpG ODN inside the body for a long period of time, (3) it can improve the cellular uptake efficiency of CpG ODN, and (4) it can deliver CpG ODN to the target tissues. Because the target cells of CpG ODN are cells of the immune system and TLR9, the receptor of CpG ODN is localized in endolysosomes, CpG ODN delivery systems are required to have qualities different from other nucleic acid drugs such as antisense DNA and small interfering RNA. Studies until now have reported various NPs as carriers for CpG ODN delivery. This review presents DNase-resistant CpG ODNs with various structures and their immunostimulatory effects and also focuses on delivery systems of CpG ODNs that utilize NPs. Because CpG ODNs interact with TLR9 and activate both the innate and the adaptive immune system, the application of CpG ODNs for the treatment of cancers, infectious diseases, and allergies holds great promise.

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“…Characteristics of pain associated with injections have been described as (1) irritation from the antiseptic used on the skin, (2) properties of the parenteral formulation, (3) sensitivity of the tissue at the injection site, (4) mechanical trauma caused by needle penetration into the tissue, and (5) distension resulting from discharge of the contents of the syringe. 4,5 Several clinical studies have shown that the application of topical anesthetic to dry oral mucosa for at least 2 minutes is effective in the reduction of injection pain. [6][7][8][9][10][11] Other studies did not find a significant difference between the use of topical anesthetic when compared with placebo or other methods.…”

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confidence: 99%

Effect of Needle Design on Pain From Dental Local Anesthetic Injections

McPherson

Dixon

Townsend

et al. 2015

Anesthesia Progress

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The purpose of this randomized, double-blind clinical study was to evaluate the effectiveness of a larger-bore compared with a standard-bore dental local anesthetic needle of the same gauge in reducing pain during inferior alveolar (IA) and long buccal (LB) nerve block injections. Twenty active duty military or Department of Defense beneficiaries undergoing dental treatment were anesthetized using a splitmouth design with 4 anesthetic dental injections. Both sides of the mouth received IA nerve block and LB nerve injections, one using the 27-gauge large-bore Septoject XL needle and other using a 27-gauge standard-bore Septoject needle. Patients rated the pain experienced with each method using a visual analogue scale (VAS). The IA injection mean VAS score and standard deviation were 38.9 6 22.7 mm and 37.1 6 22.4 mm, respectively, for the larger and standard-bore needles. The LB injection mean VAS score and standard deviation were 33.5 6 22.8 mm and 35.1 6 19.6 mm, respectively, for the larger and standard-bore needles. The data were analyzed with a paired t test (a ¼ .05). No significant difference was found between the IA (P ¼ .70) or LB injections (P ¼ .73). The use of a larger-bore 27-gauge needle did not reduce pain on injection compared with the standard-bore 27-gauge needle.

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Biopharmaceutical Considerations in Subcutaneous and Intramuscular Drug Administration

Cited by 122 publications

References 117 publications

Lymphatic Absorption of Subcutaneously Administered Proteins: Influence of Different Injection Sites on the Absorption of Darbepoetin Alfa Using a Sheep Model

Lymphatic Absorption of Subcutaneously Administered Proteins: Influence of Different Injection Sites on the Absorption of Darbepoetin Alfa Using a Sheep Model

Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system

Effect of Needle Design on Pain From Dental Local Anesthetic Injections

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