Initial Experiences with Subcutaneous Recombinant Human Hyaluronidase

Pirrello, Rosene D.; Chen, Christina Ting; Thomas, Sandra H.

doi:10.1089/jpm.2007.0037

Cited by 47 publications

(52 citation statements)

References 14 publications

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“…Hyaluronan, one of the glycosaminoglycans in the hypodermis, has a rapid turnover rate, and hyaluronidase enzymes can be used to disrupt the glycosaminoglycan matrix in a reversible manner (Frost, 2007). Recombinant human hyaluronidase (rhPH20) increases the dispersion of locally injected drugs (Bookbinder et al, 2006), has been tolerated well in clinical studies (Pirrello et al, 2007), and is being investigated for the s.c. delivery of large fluid volumes that might be required for mAb formulations (Frost, 2007;Bittner and Schmidt, 2012). An increase in rituximab bioavailability was observed after coadministration of hyaluronidase, which was in good agreement with theoretical expectations (Fig.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Subcutaneous Absorption of Rituximab in Rats

Kagan

Mager

2012

Drug Metab Dispos

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Absorption of monoclonal antibodies (mAbs) after s.c. injection results from the interplay among several kinetic processes. The aims of this study were to investigate the absorption mechanisms of rituximab in rats by using slow s.c. infusion and coadministration with nonspecific IgG or hyaluronidase, and to evaluate the predictive performance of the pharmacokinetic model previously developed to describe the nonlinear absorption behavior of mAbs. Rituximab serum concentrations were measured after s.c. coadministration with nonspecific IgG and hyaluronidase to rats. Several dose levels and different injection sites were evaluated. For the back site, 6.5-and 2.6-fold decreases in the area under the concentration-time curve were obtained after coadministration with IgG for 1 and 10 mg/kg doses compared with administration of rituximab alone. For the abdomen, only a minor reduction in concentrations was observed. Hyaluronidase increased the rate of s.c. absorption and the bioavailability (1.9-and 1.6-fold for the back and the abdomen injection of 10 mg/kg). Our previously established pharmacokinetic model provided excellent predictions of the effect of nonspecific IgG on rituximab absorption. In conclusion, the magnitude of the effect of absorption modifiers is dependent on the site of injection and the dose level of rituximab. Pharmacokinetic profiles further support the hypothesis that neonatal Fc receptormediated transport is a major determinant of s.c. absorption of mAbs.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of Subcutaneous Absorption of Rituximab in Rats

Kagan

Mager

2012

Drug Metab Dispos

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“…Finally, improved communication with young patients and their parents/caregivers is a critical factor in establishing realistic expectations and in achieving patient/parent satisfaction with the quality of medical care in the hospital and the ED. As effective as IV for fluid administration in nonemergency situations 46 Rates of fluid administration and drug absorption can be accelerated with hyaluronidase [47][48][49][50][51][52][53] Vein-sparing; fewer complications than with IV 46 Easy setup and maintenance 46,54 Cost-effective 46,54 Similar serum drug levels achieved with IO and IV 55 Access and drug delivery may be faster than with IV Risk of catheter dysfunction (eg, phlebitis, inadvertent dislodgement) 57 Risk of thrombosis 57 May take longer than other routes of venous access 56 Risk of thrombosis 56 Requires special skills that are difficult to maintain if the procedure is not done frequently Abbreviations: IV, intravenous; SC, subcutaneous; IO, intraosseous; CVC, central venous catheter.…”

Section: Discussionmentioning

confidence: 99%

“…52 Preliminary reports also suggest that rHuPH20 can enhance the SC delivery of certain medications in palliative care patients and healthy volunteers without significant adverse events. 48,53,66 …”

Section: Alternatives To IV Therapymentioning

confidence: 99%

Peripheral Difficult Venous Access in Children

Rauch

Dowd

Eldridge

et al. 2009

Clin Pediatr (Phila)

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discuss management strategies. This article summarizes the recommendations of the consensus panel for physicians. The recommendations for nurses will be published separately. Definition and Scope of the ProblemEarly identification of DVA is the first step in optimizing patient care. The consensus panel described DVA as a clinical condition in which multiple attempts and/or special interventions are anticipated or required to achieve and maintain peripheral venous access. Special interventions are defined as the use of any technique or hospital resource with the potential to improve peripheral IV insertion success rates. These include traditional methods of enhancing the visibility and palpability of peripheral veins (eg, warming the catheter site to induce vasodilation) [10][11][12] ; advanced visualization technologies such as ultrasound, transillumination, and nearinfrared lighting 2,[13][14][15] ; and enlisting designated IV specialists and/or hospital staff with extensive experience in starting pediatric IVs.16 Some children may need more invasive interventions such as intraosseous (IO) infusion, a peripherally inserted central catheter, or a central venous catheter (CVC) to achieve parenteral access.There is a dearth of clinical evidence on the incidence of DVA in pediatric patients. Studies of IV insertion success rates indicate that 5% to 33% of children require more than 2 needle sticks to achieve IV access. [1][2][3][4] Even when interventions such as transillumination and ultrasound are used, up to 15% of children still require more than 2 attempts to establish venous access.2 A recent prospective analysis of 593 insertion attempts in centers with pediatric hospitalist services showed that successful placement E stablishing peripheral intravenous (IV) access in pediatric patients can be challenging. Clinical studies show that only 53% to 76% of children are successfully cannulated on the first attempt.1-4 Multiple failed attempts are painful and upsetting for the child and distressing for family members and caregivers, 5-9 yet there are no guidelines or consensus statements on the recognition and management of this problem.In January 2008, a panel of physicians and nurses specializing in emergency medicine, anesthesia, critical care, and hospital medicine convened to discuss peripheral difficult venous access (DVA) in children. Daniel Rauch, MD, FAAP, and Laura L. Kuensting, MSN(R), RN, CPNP, cochaired the roundtable discussion, which was made possible by a grant from Baxter Healthcare, Inc. The main objectives of the meeting were to estimate the frequency of DVA in pediatric patients; describe its clinical and emotional impact on the patient, the patient's family, and clinicians; develop terminology that accurately describes the condition; review the factors that help identify children with DVA; and

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“…In clinical studies the intradermal delivery was generally well tolerated (although some transient, localized wheal formation and redness were noticed at injection sites), but the potential effects of high level or repetitive exposure of protein drugs such as insulin on the lymphatics and immune system need full investigation (90,91). Another area of research focuses on the combination of available insulin products with a human recombinant hyaluronidase, which facilitates the local dispersion and absorption of co-administered molecules (92,93). The human recombinant hyaluronidase is a highly purified neutral pH-active enzyme that depolymerizes hyaluronan in the hypodermis under physiologic conditions.…”

Section: Current Ultrafast Insulin Formulationsmentioning

confidence: 99%